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Introduction: tuberculosis remains a major public health problem, with continuing high levels of prevalence, and mortality. In Niger, the incidence of tuberculosis remains high. This study aims to investigate the epidemiology of pulmonary tuberculosis at the National Anti-Tuberculosis Center of Niamey in Niger. Methods: this study used a quantitative approach with a retrospective and descriptive design. Data were obtained from positive pulmonary tuberculosis cases detected by microscopy on Ziehl-Neelsen stained sputum at the National Anti-Tuberculosis Center (NATC) in Niamey, Niger covered the period between June 2017 and January 2020. 955 pulmonary TB patients were recorded whose diagnosis was based either on clinical-radiological arguments (thus negative microscopy) or positive microscopy. This form was used to collect data recorded in the clinical case registers, registers, and Excel files of the GeneXpert platform of the NATC laboratory. Results: eighty-nine-point eleven percent (89.11%) of the patients were microscopy-positive. Among the study population, men were the most affected by tuberculosis with 80.03%. The 25-34 age group, representing 23.77%, was the most affected. 6.93% of patients were co-infected with tuberculosis and HIV. All patients were put on treatment, with a therapeutic success rate of 72.38% and a therapeutic failure rate of 10.95%. Among the cases of therapeutic failure, 80.90% had Mycobacterium tuberculosis complex detected and 27.14% were resistant to Rifampicin. Conclusion: Niger continues to have a tuberculosis epidemic which requires monitoring. Improving the diagnostic system for more effective management of the disease is important for appropriate diagnosis and treatment.
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Antituberculosos , Mycobacterium tuberculosis , Tuberculosis Pulmonar , Humanos , Estudios Retrospectivos , Masculino , Niger/epidemiología , Femenino , Adulto , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/diagnóstico , Antituberculosos/farmacología , Antituberculosos/administración & dosificación , Adulto Joven , Persona de Mediana Edad , Mycobacterium tuberculosis/aislamiento & purificación , Mycobacterium tuberculosis/efectos de los fármacos , Adolescente , Resultado del Tratamiento , Niño , Infecciones por VIH/epidemiología , Infecciones por VIH/tratamiento farmacológico , Preescolar , Anciano , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Esputo/microbiología , Prevalencia , Coinfección/epidemiología , Coinfección/tratamiento farmacológico , Lactante , IncidenciaRESUMEN
Culturing and genomic sequencing of Mycobacterium tuberculosis (MTB) from tuberculosis (TB) cases is the basis for many research and clinical applications. The alternative, culture-free sequencing from diagnostic samples, is promising but poses challenges to obtain and analyse the MTB genome. Paradoxically, culture is assumed to impose a diversity bottleneck, which, if true, would entail unexplored consequences. To unravel this paradox we generate high-quality genomes of sputum-culture pairs from two different settings after developing a workflow for sequencing from sputum and a tailored bioinformatics analysis. Careful downstream comparisons reveal sources of sputum-culture incongruences due to false positive/negative variation associated with factors like low input MTB DNA or variable genomic depths. After accounting for these factors, contrary to the bottleneck dogma, we identify a 97% variant agreement within sputum-culture pairs, with a high correlation also in the variants' frequency (0.98). The combined analysis from five different settings and more than 100 available samples shows that our results can be extrapolated to different TB epidemic scenarios, demonstrating that for the cases tested culture accurately mirrors clinical samples.
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Variación Genética , Mycobacterium tuberculosis , Esputo , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Esputo/microbiología , Humanos , Tuberculosis/microbiología , Tuberculosis/diagnóstico , Genoma Bacteriano , ADN Bacteriano/genética , Tuberculosis Pulmonar/microbiología , Tuberculosis Pulmonar/diagnósticoRESUMEN
Tuberculosis (TB) is the leading cause of mortality among infectious diseases globally. Effectively managing TB requires early identification of individuals with TB disease. Resource-constrained settings often lack skilled professionals for interpreting chest X-rays (CXRs) used in TB diagnosis. To address this challenge, we developed "DecXpert" a novel Computer-Aided Detection (CAD) software solution based on deep neural networks for early TB diagnosis from CXRs, aiming to detect subtle abnormalities that may be overlooked by human interpretation alone. This study was conducted on the largest cohort size to date, where the performance of a CAD software (DecXpert version 1.4) was validated against the gold standard molecular diagnostic technique, GeneXpert MTB/RIF, analyzing data from 4363 individuals across 12 primary health care centers and one tertiary hospital in North India. DecXpert demonstrated 88% sensitivity (95% CI 0.85-0.93) and 85% specificity (95% CI 0.82-0.91) for active TB detection. Incorporating demographics, DecXpert achieved an area under the curve of 0.91 (95% CI 0.88-0.94), indicating robust diagnostic performance. Our findings establish DecXpert's potential as an accurate, efficient AI solution for early identification of active TB cases. Deployed as a screening tool in resource-limited settings, DecXpert could enable early identification of individuals with TB disease and facilitate effective TB management where skilled radiological interpretation is limited.
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Programas Informáticos , Humanos , India/epidemiología , Femenino , Masculino , Adulto , Persona de Mediana Edad , Diagnóstico por Computador/métodos , Tuberculosis/diagnóstico , Tuberculosis/diagnóstico por imagen , Tuberculosis Pulmonar/diagnóstico por imagen , Tuberculosis Pulmonar/diagnóstico , Sensibilidad y Especificidad , Adulto Joven , Adolescente , Radiografía Torácica/métodos , AncianoRESUMEN
OBJECTIVE: To evaluate the effectiveness of a machine learning based on computed tomography (CT) radiomics to distinguish nontuberculous mycobacterial pulmonary disease (NTM-PD) from pulmonary tuberculosis (PTB). METHODS: In this retrospective analysis, medical records of 99 individuals afflicted with NTM-PD and 285 individuals with PTB in Zhejiang Chinese and Western Medicine Integrated Hospital were examined. Random numbers generated by a computer were utilized to stratify the study cohort, with 80% designated as the training cohort and 20% as the validation cohort. A total of 2153 radiomics features were extracted using Python (Pyradiomics package) to analyse the CT characteristics of the large disease areas. The identification of significant factors was conducted through the least absolute shrinkage and selection operator (LASSO) regression. The following four supervised learning classifier models were developed: random forest (RF), support vector machine (SVM), logistic regression (LR), and extreme gradient boosting (XGBoost). For assessment and comparison of the predictive performance among these models, receiver-operating characteristic (ROC) curves and the areas under the ROC curves (AUCs) were employed. RESULTS: The Student's t-test, Levene test, and LASSO algorithm collectively selected 23 optimal features. ROC analysis was then conducted, with the respective AUC values of the XGBoost, LR, SVM, and RF models recorded to be 1, 0.9044, 0.8868, and 0.7982 in the training cohort. In the validation cohort, the respective AUC values of the XGBoost, LR, SVM, and RF models were 0.8358, 0.8085, 0.87739, and 0.7759. The DeLong test results noted the lack of remarkable variation across the models. CONCLUSION: The CT radiomics features can help distinguish between NTM-PD and PTB. Among the four classifiers, SVM showed a stable performance in effectively identifying these two diseases.
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Aprendizaje Automático , Infecciones por Mycobacterium no Tuberculosas , Tomografía Computarizada por Rayos X , Tuberculosis Pulmonar , Humanos , Estudios Retrospectivos , Tuberculosis Pulmonar/diagnóstico por imagen , Tuberculosis Pulmonar/diagnóstico , Tomografía Computarizada por Rayos X/métodos , Masculino , Femenino , Persona de Mediana Edad , Infecciones por Mycobacterium no Tuberculosas/diagnóstico por imagen , Infecciones por Mycobacterium no Tuberculosas/microbiología , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Diagnóstico Diferencial , Anciano , Adulto , Algoritmos , Curva ROC , Máquina de Vectores de Soporte , RadiómicaRESUMEN
INTRODUCTION: The WHO estimates a gap of about 30% between the incident (10.6 million) and notified (7.5 million) cases of tuberculosis (TB). Combined with the growing recognition in prevalence surveys of the high proportion of cases identified who are asymptomatic or paucisymptomatic, these data underscore how current symptom screening approaches and use of diagnostic tests with suboptimal performance on sputum miss large numbers of cases. Thus, the development of sputum-free biomarker-based tests for diagnosis is becoming necessary, which the WHO has already identified as a priority for new TB diagnostics.The objective of this study is to evaluate a combination of exhaled breath condensate (EBC) samples and mycobacterial lipoarabinomannan (LAM) as point-of-care (POC) assays to identify TB patients. METHODS AND ANALYSIS: This prospective diagnostic accuracy study is conducted at the TB Screening and Treatment Centre of International Center for Diarrhoeal Disease Research, Bangladesh, on a cohort of adults and adolescents >11 years of age. A total of 614 individuals with presumptive pulmonary TB based on TB signs, symptoms and radiography are being recruited from 28 August 2023. Spot sputum is collected for standard reference testing (L-J culture, GeneXpert MTB/Rif, acid-fast Bacilli microscopy) to fine-tune categorisation of TB disease status for each participant, defined as (1) definite TB (at least one positive standard reference test); (2) probable TB (not microbiologically confirmed but under TB treatment); (3) possible TB (no TB treatment but signs, symptoms and radiography suggestive of TB); (4) other respiratory disease (microbiologically not confirmed and no radiography presenting abnormalities compatible with TB); and (5) unknown (no microbiological evidence with normal/no TB abnormalities with radiography). Urine and EBC specimens will be subjected to LAM POC testing and biobanked for further investigation. Statistical analyses will include an assessment of diagnostic accuracy by constructing receiver operating curves and calculating sensitivity and specificity, as well as post-test probabilities. ETHICS AND DISSEMINATION: The study protocol was approved by the Research Review Committee as well as the Ethical Review Committee of icddr,b and recorded under a protocol reference number, PR-2301. Results will be submitted to open-access peer-reviewed journals, presented at academic meetings, and shared with national and international policymaking bodies.
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Pruebas Respiratorias , Lipopolisacáridos , Tuberculosis Pulmonar , Humanos , Lipopolisacáridos/análisis , Tuberculosis Pulmonar/diagnóstico , Pruebas Respiratorias/métodos , Estudios Prospectivos , Biomarcadores/análisis , Bangladesh , Adulto , Pruebas en el Punto de Atención , Sensibilidad y Especificidad , Sistemas de Atención de Punto , Masculino , Femenino , Adolescente , Mycobacterium tuberculosis/aislamiento & purificación , Esputo/microbiologíaRESUMEN
Background: microRNAs (miRNAs) were recognized as a promising source of diagnostic biomarker. Herein, we aim to evaluate the performance of an ultrasensitive method for detecting serum miRNAs using single molecule arrays (Simoa). Methods: In this study, candidate miRNAs were trained and tested by RT-qPCR in a cohort of PTB patients. Besides that, ultrasensitive serum miRNA detection were developed using the Single Molecule Array (Simoa) platform. In this ultra-sensitive sandwich assay, two target-specific LNA-modified oligonucleotide probes can be simply designed to be complementary to the half-sequence of the target miRNA respectively. We characterized its analytical performance and measured miRNAs in the serum of patients with pulmonary tuberculosis and healthy individuals. Results: We identified a five signature including three upregulated (miR-101, miR-196b, miR-29a) and two downregulated (miR-320b, miR-99b) miRNAs for distinguishing PTB patients from HCs, and validated in our 104 PTB patients. On the basis of Simoa technology, we developed a novel, fully automated digital analyser, which can be used to directly detect miRNAs in serum samples without pre-amplification. We successfully detected miRNAs at femtomolar concentrations (with limits of detection [LODs] ranging from 0.449 to 1.889 fM). Simoa-determined serum miR-29a and miR-99b concentrations in patients with PTB ((median 6.06 fM [range 0.00-75.22]), (median 2.53 fM [range 0.00-24.95]), respectively) were significantly higher than those in HCs ((median 2.42 fM [range 0.00-28.64]) (P < 0.05), (median 0.54 fM [range 0.00-9.12] (P < 0.0001), respectively). Serum levels of miR-320b were significantly reduced in patients with PTB (median 2.11 fM [range 0.00-39.30]) compared with those in the HCs (median 4.76 fM [range 0.00-25.10]) (P < 0.001). A combination of three miRNAs (miR-29a, miR-99b, and miR-320b) exhibited a good capacity to distinguish PTB from HCs, with an area under the curve (AUC) of 0.818 (sensitivity: 83.9%; specificity: 79.7%). Conclusions: This study benchmarks the role of Simoa as a promising tool for monitoring miRNAs in serum and offers considerable potential as a non-invasive platform for the early diagnosis of PTB.
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Biomarcadores , MicroARNs , Tuberculosis Pulmonar , Humanos , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/sangre , Tuberculosis Pulmonar/genética , Masculino , Femenino , MicroARNs/sangre , MicroARNs/genética , Persona de Mediana Edad , Adulto , Biomarcadores/sangre , Anciano , MicroARN Circulante/sangre , MicroARN Circulante/genéticaRESUMEN
The aim of this study was to explore the related factors linked to the development and infectivity of tuberculosis. This was achieved by comparing the clinical characteristics of patients with pulmonary tuberculosis (TB) who tested positive in smear Mycobacterium tuberculosis tests with this who tested negative in smear mycobacterium tests but positive in sputum Gene Xpert tests. We gathered clinical data of 1612 recently hospitalized patients diagnosed with pulmonary tuberculosis who tested positive either in sputum Gene-Xpert test or sputum smear Mycobacterium tuberculosis tests. The data was collected from January 1, 2018 to August 5, 2023, at Sichuan Provincial People's Hospital. We conducted separately analyzes and comparisons of the clinical characteristics between the two groups of patients, aiming to discussed the related factors influencing the development and infectivity of tuberculosis. In comparison to the GeneXpert positive group, the sputum smear positive group exhibited a higher proportion of elderly patients (aged 75-89) and individuals classified as underweight (BMI < 18.5 kg/m2). Furthermore, this group was more prone to experiencing symptoms such as weight loss, coughing and sputum production, hemoptysis, shortness of breath, and difficulty breathing. Moreover, they are also more likely to develop extrapulmonary tuberculosis, such as tuberculous meningitis, tuberculous pleurisy, and tuberculous peritonitis. These clinical features, when present, not only increase the likelihood of a positive result in sputum smear tests but also suggest a high infectivity of pulmonary tuberculosis. Elderly individuals (aged 75 to 89) who are underweight (BMI < 18.5 kg/m2), display symptom of cough, expectoration, hemoptysis and dyspnea-particularly cough and expectoration-and those with extra pulmonary tuberculosis serve as indicators of highly infectious pulmonary tuberculosis patients. These patients may present with more severe condition, carrying a higher bacteria, and being more prone to bacterial elimination. Identification of these patients is crucial, and prompt actions such as timely and rapid isolation measures, cutting off transmission routes, and early empirical treatment of tuberculosis are essential to control the development of the disease.
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Mycobacterium tuberculosis , Esputo , Tuberculosis Pulmonar , Humanos , Esputo/microbiología , Masculino , Femenino , Mycobacterium tuberculosis/aislamiento & purificación , Anciano , Persona de Mediana Edad , Tuberculosis Pulmonar/microbiología , Tuberculosis Pulmonar/diagnóstico , Adulto , Anciano de 80 o más Años , Adulto Joven , AdolescenteRESUMEN
Sarcoidosis and tuberculosis (TB) are two granulomatous diseases that often share overlapping clinical features, including uveitis. We measured 368 inflammation-related proteins in serum in both diseases, with and without uveitis from two distinct geographically separated cohorts: sarcoidosis from the Netherlands and TB from Indonesia. A total of 192 and 102 differentially expressed proteins were found in sarcoidosis and active pulmonary TB compared to their geographical healthy controls, respectively. While substantial overlap exists in the immune-related pathways involved in both diseases, activation of B cell activating factor (BAFF) signaling and proliferation-inducing ligand (APRIL) mediated signaling pathways was specifically associated with sarcoidosis. We identified a B-lymphocyte activation signature consisting of BAFF, TNFRSF13B/TACI, TRAF2, IKBKG, MAPK9, NFATC1, and DAPP1 that was associated with sarcoidosis, regardless of the presence of uveitis. In summary, a difference in B-lymphocyte activation is a key discriminative immunological feature between sarcoidosis/ocular sarcoidosis (OS) and TB/ocular TB (OTB).
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Linfocitos B , Activación de Linfocitos , Sarcoidosis , Humanos , Sarcoidosis/inmunología , Sarcoidosis/sangre , Sarcoidosis/diagnóstico , Linfocitos B/inmunología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Países Bajos/epidemiología , Tuberculosis Pulmonar/inmunología , Tuberculosis Pulmonar/sangre , Tuberculosis Pulmonar/diagnóstico , Uveítis/inmunología , Uveítis/sangre , Uveítis/diagnóstico , Factor Activador de Células B/sangre , Indonesia , Biomarcadores/sangre , Tuberculosis/inmunología , Tuberculosis/sangre , Tuberculosis/diagnósticoRESUMEN
A man in his early 50s with previously treated pulmonary tuberculosis (TB) presented with a 3-month history of cough, expectoration and progressive breathlessness, accompanied by significant weight loss. Examination revealed tachycardia, tachypnoea, hypoxaemia and unilateral diminished breath sounds. Investigations showed anaemia, leucocytosis and a homogeneous opacity on the left side of the CXR. ECG and echocardiography suggested pulmonary thromboembolism (PTE). A CT pulmonary angiogram confirmed a chronic embolus and a severely fibrosed left lung. A comprehensive thrombophilia workup yielded normal results and the PTE was attributed to his history of TB. Sputum analysis confirmed reactivated TB, leading to the initiation of antitubercular therapy. The patient improved clinically with plans for a repeat CT pulmonary angiography to assess the need for pulmonary thromboendarterectomy after completing TB treatment. This case highlights the possible association of TB and PTE, its management and why it should be considered as a differential diagnosis in patients with a history of TB presenting with exacerbated breathlessness.
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Antituberculosos , Embolia Pulmonar , Tuberculosis Pulmonar , Humanos , Masculino , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/diagnóstico , Embolia Pulmonar/complicaciones , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/diagnóstico por imagen , Persona de Mediana Edad , Diagnóstico Diferencial , Antituberculosos/uso terapéutico , Angiografía por Tomografía Computarizada , Disnea/etiología , Disnea/diagnóstico , EcocardiografíaRESUMEN
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
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
BACKGROUND: The latent tuberculosis infection (LTBI) burden is still unclear in schoolchildren and adolescents in China. Previous study and daily surveillance data indicate a LTBI detection gap. The research objective was to evaluate the LTBI burden and detection gap among schoolchildren and adolescents in China. METHODS: A cross-sectional study was conducted among 69,667 schoolchildren and adolescents in Chongqing, China between September 2022 and December 2023 implemented by Chongqing Municipal Institute of Tuberculosis using tuberculin skin test (TST) and creation tuberculin skin test (C-TST). To evaluate the LTBI detection gap, the pulmonary tuberculosis (PTB) screening data implemented by Chongqing Municipal Institute of Tuberculosis have been compared with the data in 2021 implemented by community-level medical and health care institutions. RESULTS: The LTBI prevalence rate using TST and C-TST implemented by Chongqing Municipal Institute of Tuberculosis was 12.8% (95%CI, 12.5-13%) and 6.4% (95%CI, 6-6.8%) respectively. The LTBI prevalence rate by Chongqing Municipal Institute of Tuberculosis was 9.6% higher than that by community-level medical and health care institutions (χ2 = 2931.9, P < 0.001). CONCLUSIONS: The LTBI detection gap existed among schoolchildren and adolescents in Chongqing, and it also may exist in other similar countries and regions. National screening strategy needs improvement. Regular training and quality assurance could improve the performance of TST and C-TST and close the detection gap of LTBI.
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Tuberculosis Latente , Tamizaje Masivo , Prueba de Tuberculina , Humanos , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/epidemiología , Estudios Transversales , China/epidemiología , Adolescente , Niño , Masculino , Femenino , Prevalencia , Tamizaje Masivo/métodos , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/diagnósticoRESUMEN
Diagnosis of pulmonary tuberculosis (TB) relies on a sputum sample, which cannot be obtained from all symptomatic individuals. Mycobacterium tuberculosis (Mtb) transrenal DNA (trDNA) has been detected in urine, an easily obtainable, noninvasive, alternative sample type. However, reported sensitivities have been variable and likely depend on collection and assay procedures and aspects of trDNA biology. We analyzed three serial urine samples from each of 75 adults with culture-confirmed pulmonary TB disease in Lima, Peru for detection of trDNA using short-fragment real-time PCR. Additionally, we examined host, urine, and sampling factors associated with detection. Overall per-sample sensitivity was 38 % (95 % Confidence Interval [CI] 30-45 %). On an individual level (i.e., any of the three samples positive), sensitivity was 73 % (95 % CI: 62-83 %). Sensitivity was highest among samples from patients with smear-positive TB, 92 % (95 % CI: 62-100 %). Specificity from a single sample from each of 10 healthy controls was 100 % (95 % CI: 69-100 %). Adjusting our assay positivity threshold increased individual-level sensitivity to 88 % (95 % CI: 78-94 %) overall without affecting the specificity. We did not find associations between Mtb trDNA detection and individual characteristics or urine sample characteristics. Overall, our results support the potential of trDNA detection for TB diagnosis.
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ADN Bacteriano , Mycobacterium tuberculosis , Tuberculosis Pulmonar , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Adulto , Femenino , Perú/epidemiología , Masculino , ADN Bacteriano/orina , ADN Bacteriano/genética , Tuberculosis Pulmonar/orina , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/microbiología , Persona de Mediana Edad , Adulto Joven , Reacción en Cadena en Tiempo Real de la Polimerasa , Valor Predictivo de las Pruebas , Urinálisis/métodos , Estudios de Casos y Controles , Reproducibilidad de los Resultados , AncianoRESUMEN
BACKGROUND: Tuberculosis (TB), a major cause of disease and antimicrobial resistance, is spread via aerosols. Aerosols have diagnostic potential and airborne-microbes other than Mycobacterium tuberculosis complex (MTBC) may influence transmission. We evaluated whether PneumoniaCheck (PMC), a commercial aerosol collection device, captures MTBC and the aeromicrobiome of people with TB. METHODS: PMC was done in sputum culture-positive people (≥ 30 forced coughs each, n = 16) pre-treatment and PMC air reservoir (bag, corresponding to upper airways) and filter (lower airways) washes underwent Xpert MTB/RIF Ultra (Ultra) and 16S rRNA gene sequencing (sequencing also done on sputum). In a subset (n = 6), PMC microbiota (bag, filter) was compared to oral washes and bronchoalveolar lavage fluid (BALF). FINDINGS: 54% (7/13) bags and 46% (6/14) filters were Ultra-positive. Sequencing read counts and microbial diversity did not differ across bags, filters, and sputum. However, microbial composition in bags (Sphingobium-, Corynebacterium-, Novosphingobium-enriched) and filters (Mycobacterium-, Sphingobium-, Corynebacterium-enriched) each differed vs. sputum. Furthermore, sequencing only detected Mycobacterium in bags and filters but not sputum. In the subset, bag and filter microbial diversity did not differ vs. oral washes or BALF but microbial composition differed. Bags vs. BALF were Sphingobium-enriched and Mycobacterium-, Streptococcus-, and Anaerosinus-depleted (Anaerosinus also depleted in filters vs. BALF). Compared to BALF, none of the aerosol-enriched taxa were enriched in oral washes or sputum. INTERPRETATION: PMC captures aerosols with Ultra-detectable MTBC and MTBC is more detectable in aerosols than sputum by sequencing. The aeromicrobiome is distinct from sputum, oral washes and BALF and contains differentially-enriched lower respiratory tract microbes.
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Aerosoles , Líquido del Lavado Bronquioalveolar , Tos , Mycobacterium tuberculosis , ARN Ribosómico 16S , Esputo , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Aerosoles/análisis , Esputo/microbiología , Tos/microbiología , Masculino , ARN Ribosómico 16S/genética , Adulto , Femenino , Líquido del Lavado Bronquioalveolar/microbiología , Persona de Mediana Edad , Microbiota , Microbiología del Aire , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/microbiología , Tuberculosis/diagnóstico , Tuberculosis/microbiología , Manejo de Especímenes/métodos , Manejo de Especímenes/instrumentación , Anciano , Adulto JovenRESUMEN
Introduction: The lungs are most commonly involved in tuberculosis, but infection can also involve other organs through lymphohematogenous dissemination. The clinical presentation of disseminated tuberculosis is variable. Diagnosis is difficult, because clinical manifestations are diverse, more than 50% of patients present late, because microbiological testing relies on invasive procedures for mycobacterial culture and supportive histopathology. Case report: A 30-year-old male patient, deprived of his liberty, with no co-morbidities, was admitted to the hospital for severe pain in the left wrist, with a previous history of having received systemic glucocorticoids for 7 months. He developed clinical symptoms of pulmonary tuberculosis, in the pleura, in the joint of the left wrist and in the left testicle, and tests confirmed the presence of M. tuberculosis. He underwent surgery on the wrist and testicle and was also treated for susceptible tuberculosis. Concomitant sequelae of iatrogenic Cushing's disease, chronic anemia and chronic inactive proctitis were diagnosed. Conclusions: Diagnosis of disseminated tuberculosis was difficult due to the non-specific clinical picture, limitations of confirmatory diagnostic tools and timely specialized evaluations. Prolonged use of systemic corticosteroids may have played a role in the dissemination of tuberculosis.
Introducción: Los pulmones son más afectados en la tuberculosis. La infección también puede comprometer a otros órganos a través de la diseminación linfohematógena. La presentación del cuadro clínico de la tuberculosis diseminada es variable. El diagnóstico es difícil, porque las manifestaciones clínicas son diversas. Más del 50% de los pacientes acuden tardíamente, porque las pruebas microbiológicas dependen de procedimientos invasivos para el cultivo de micobacterias y la histopatología de apoyo. Caso clínico: Paciente varón de 30 años, persona privada de su libertad, sin comorbilidades, ingresó al hospital por dolor intenso en muñeca izquierda, con historia previa de haber recibido glucocorticoides sistémicos durante siete meses. Desarrolló cuadro clínico de tuberculosis pulmonar en pleura, en articulación de la muñeca izquierda y en testículo izquierdo. En los análisis se confirmó presencia de . Fue intervenido quirúrgicamente en muñeca y en el testículo. Además, recibió tratamiento para tuberculosis sensible. Concomitantemente se diagnosticó secuelas de Cushing iatrogénico, anemia crónica y proctitis crónica inactiva. Conclusiones: El diagnóstico de tuberculosis diseminada fue difícil debido al cuadro clínico inespecífico, a las limitaciones de herramientas de diagnóstico confirmatorio y a las evaluaciones especializadas en forma oportuna. El uso prolongado de corticoides sistémicos habría influido en la diseminación de la tuberculosis.
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Diagnóstico Tardío , Humanos , Masculino , Adulto , Tuberculosis Pulmonar/diagnóstico , Mycobacterium tuberculosis/aislamiento & purificación , Glucocorticoides/administración & dosificación , Glucocorticoides/uso terapéutico , Tuberculosis Miliar/diagnósticoRESUMEN
BACKGROUND: Tuberculosis often presents on imaging in the form of a solitary nodule, sometimes accompanied by elevated CEA, which is clinically difficult to differentiate from lung cancer and prone to misdiagnosis. METHODS: Lung tissue taken by lung biopsy and sent for NGS and Xpert MTB/RIF finally led to the definitive diag-nosis of nodular foci in the upper lobe of the left lung caused by tuberculosis. RESULTS: Enhanced CT of the chest showed nodular foci in the upper lobe of the left lung. Initially the nodules were thought to be malignant, but after a series of tests, were finally confirmed to be tuberculosis. CONCLUSIONS: In patients with lung disease, when chest imaging reveals a space-occupying lesion accompanied by an elevated CEA level, a comprehensive analysis of the type of lung disease, the patient's age, and comorbidities should be performed before final diagnosis to avoid misdiagnosis and delay in appropriate treatment.
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Antígeno Carcinoembrionario , Errores Diagnósticos , Neoplasias Pulmonares , Humanos , Antígeno Carcinoembrionario/sangre , Neoplasias Pulmonares/diagnóstico , Masculino , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/sangre , Diagnóstico Diferencial , Tomografía Computarizada por Rayos X , Persona de Mediana Edad , Pulmón/patología , Pulmón/diagnóstico por imagen , FemeninoRESUMEN
The spatial delays of pulmonary tuberculosis (PTB) have been less explored. In this study, a total of 151,799 notified PTB cases were included, with median patient and diagnostic delays of 15 [interquartile range (IOR), 4-35] and 2 (IOR, 0-8) days, respectively. The spatial autocorrelation analysis and spatial-temporal scan statistics were used to determine the clusters, indicating that the regions in the southwestern and northeastern parts of Zhejiang Province exhibited high rates of long-term patient delay (LPD, delay ≥ 15 days) and long-term diagnostic delay (LDD, delay ≥ 2 days). Besides, the Mantel test indicated a moderately positive correlation between public awareness of suspicious symptoms and the LPD rate in 2018 (Mantel's r = 0.4, P < 0.05). These findings suggest that PTB delays can reveal deficiencies in public health education and the healthcare system. Also, it is essential to explore methods to shift PTB knowledge towards real changes in attitude and behavior to minimize patient delay. Addressing these issues will be crucial for improving public health outcomes related to PTB in Zhejiang Province.
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Diagnóstico Tardío , Tuberculosis Pulmonar , Humanos , China/epidemiología , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/diagnóstico , Femenino , Masculino , Adulto , Diagnóstico Tardío/estadística & datos numéricos , Persona de Mediana Edad , Análisis Espacio-Temporal , Adulto Joven , Conocimientos, Actitudes y Práctica en Salud , Adolescente , Encuestas y Cuestionarios , AncianoRESUMEN
BACKGROUND: Microbiological diagnosis of pulmonary tuberculosis (PTB) is hampered by a low pathogen burden, low compliance and unreliable sputum sampling. Although endobronchial ultrasound-guided transbronchoscopic lung biopsy (EBUS-TBLB) has been found to be useful for the assessment of intrapulmonary nodules in adults, few data are available for the clinical diagnosis of pulmonary tuberculosis. Here, we evaluated EBUS-TBLB as a diagnostic procedure in adult patients with radiologically suspected intrapulmonary tuberculous nodules. METHODS: This was a retrospective analysis of patients admitted with pulmonary nodules between January 2022 and January 2023 at Hangzhou Red Cross Hospital. All patients underwent EBUS-TBLB, and lung biopsy samples were obtained during hospitalization. All samples were tested for Mycobacterium tuberculosis using acidâfast smears, Bactec MGIT 960, Xpert MTB/RIF, next-generation sequencing (NGS), and DNA (TBâDNA) and RNA (TBâRNA). The concordance between different diagnostic methods and clinical diagnosis was analysed via kappa concordance analysis. The diagnostic efficacy of different diagnostic methods for PTB was analysed via ROC curve. RESULTS: A total of 107 patients were included in this study. Among them, 86 patients were diagnosed by EBUS-TBLB, and the overall diagnostic rate was 80.37%. In addition, 102 enrolled patients had benign lesions, and only 5 were diagnosed with lung tumours. Univariate analysis revealed that the diagnostic rate of EBUS-TBLB in pulmonary nodules was related to the location of the probe. The consistency analysis and ROC curve analysis revealed that NGS had the highest concordance with the clinical diagnosis results (agreement = 78.50%, κ = 0.558) and had the highest diagnostic efficacy for PTB (AUC = 0.778). In addition, Xpert MTB/RIF + NGS had the highest concordance with the clinical diagnosis results (agreement = 84.11%, κ = 0.667) and had the highest efficacy in the diagnosis of PTB (AUC = 0.826). CONCLUSION: EBUS-TBLB is a sensitive and safe method for the diagnosis of pathological pulmonary nodules. Xpert MTB/RIF combined with NGS had the highest diagnostic efficacy and can be used in the initial diagnosis of PTB.
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Broncoscopía , Mycobacterium tuberculosis , Tuberculosis Pulmonar , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/patología , Tuberculosis Pulmonar/microbiología , Broncoscopía/métodos , Mycobacterium tuberculosis/aislamiento & purificación , Adulto , Anciano , Pulmón/patología , Pulmón/microbiología , Pulmón/diagnóstico por imagen , Biopsia Guiada por Imagen/métodos , Sensibilidad y EspecificidadRESUMEN
Tongue swabs hold promise as a non-invasive sample for diagnosing tuberculosis (TB). However, their utility as replacements for sputum has been limited by their varied diagnostic performance in PCR assays compared to sputum. The use of silica-based DNA extraction methods may limit sensitivity due to incomplete lysis of Mycobacterium tuberculosis (MTB) cells and co-extraction of non-target nucleic acid, which may inhibit PCR. Specificity may also be compromised because these methods are labor-intensive and prone to cross-contamination. To address these limitations, we developed a sample preparation method that combines sonication for MTB lysis and a sequence-specific MTB DNA capture method using hybridization probes immobilized on magnetic beads. In spiked tongue swabs, our hybridization capture method demonstrated a 100-fold increase in MTB DNA yield over silica-based Qiagen DNA extraction and ethanol precipitation. In a study conducted on clinical samples from South Africa, our protocol had 74% (70/94) sensitivity and 98% (41/42) specificity for detecting active pulmonary TB with sputum Xpert MTB/RIF Ultra as the reference standard. While hybridization capture did not show improved sensitivity over Qiagen DNA extraction and ethanol precipitation, it demonstrated better specificity than previously reported methods and was easier to perform. With integration into point-of-care platforms, these strategies have the potential to help enable rapid non-sputum-based TB diagnosis across key underserved patient populations.