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1.
Rev Soc Bras Med Trop ; 54: e07552020, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33605382

RESUMEN

INTRODUCTION: The intensification of research and innovation with the creation of networks of rapid and effective molecular tests as strategies for the end of tuberculosis are essential to avoid late diagnosis and for the eradication of the disease. We aimed to evaluate the cost-effectiveness of Xpert®MTB/RIF (Xpert) in the diagnosis of drug-resistant tuberculosis in reference units, in scenarios with and without subsidies, and the respective cost adjustment for today. METHODS: The analyses were performed considering as criterion of effectiveness, negative culture or clinical improvement in the sixth month of follow-up. The comparison was performed using two diagnostic strategies for the drug susceptibility test (DST), BactecTMMGITTM960 System, versus Xpert. The cost effectiveness and incremental cost-effectiveness ratio (ICER) were calculated and dollar-corrected for American inflation (US$ 1.00 = R$ 5,29). RESULTS: Subsidized Xpert had the lowest cost of US$ 33.48 (R$67,52) and the highest incremental average efficiency (13.57), thus being a dominated analysis. After the inflation was calculated, the mean cost was DST-MGIT=US$ 74.85 (R$ 396,73) and Xpert = US$ 37.33 (R$197,86) with subsidies. CONCLUSIONS: The Xpert in the diagnosis of TB-DR in these reference units was cost-effective with subsidies. In the absence of a subsidy, Xpert in TB-DR is not characterized as cost effective. This factor reveals the vulnerability of countries dependent on international organizations' subsidy policies.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis , Análisis Costo-Beneficio , Humanos , Mycobacterium tuberculosis/genética , Sensibilidad y Especificidad , Tuberculosis/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico
2.
Zhonghua Jie He He Hu Xi Za Zhi ; 44(2): 96-100, 2021 Feb 12.
Artículo en Chino | MEDLINE | ID: mdl-33535323

RESUMEN

Objective: To investigate the diagnostic value of metagenomic next generation sequencing(mNGS)for different types of tuberculosis(TB). Methods: A retrospective analysis was performed on suspected TB patients admitted to Shanghai Pulmonary Hospital from January 1, 2019 to December 31, 2019. The patients underwent mNGS test, acid-fast staining smear, Mycobacterium tuberculosis (MTB) culture and Xpert MTB/RIF(Xpert). A total of 205 TB suspects were finally included, including 120 males and 85 females, with a median age of 34 (16, 70) years. There were 165 cases of TB, including 92 males and 73 females, with a median age of 30 (12, 67) years. There were 40 non-TB patients, 28 males and 12 females, with a median age of 44.6 (24, 78) years, including 28 cases of infectious diseases and 12 cases of malignant tumors. With the final diagnosis as the reference standard, the diagnostic efficiency of mNGS in different types of tuberculosis (including pulmonary tuberculosis and extrapulmonary tuberculosis) and differences in diagnostic sensitivities between mNGS and other detection methods were calculated, respectively. P<0.05 was considered to be statistically different. Results: With clinical diagnosis as the reference standard, the sensitivity of mNGS to diagnose TB in this study was 60% (99/165, 95%CI: 0.53-0.67), and the specificity was 100% (40/40, 95%CI 0.90-1.00). The positive predictive value was 100% (99/99, 95%CI: 0.95-1.00), and the negative predictive value was 37.74% (40/106, 95%CI: 0.29-0.48). The sensitivity of mNGS in TB was 60% (99/165), higher than that of smear (10.9%, 18/165), Xpert(43.64%, 72/165) and culture (23.03%, 38/165). All the differences were statistically significant (P=0.00). The sensitivity of mNGS in pulmonary TB was 59%(59/100), which was significantly higher than that of smear (15%, 15/100) and culture (26%, 26/100), all P<0.001, but the difference was not statistically significant compared with Xpert (52%,52/100, P=0.09). In the extrapulmonary tuberculosis (EPTB), the sensitivity of mNGS was 61.54% (40/65), higher than that of acid fast staining(4.62%,3/65), Xpert (30.77%, 20/65)and culture (18.45%, 12/65). All the differences were statistically significant (all P<0.001). Conclusion: The mNGS was rapid and efficient in detection of MTB, and was superior to other traditional diagnostic methods for TB, especially for EPTB.


Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Metagenómica , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis/diagnóstico , Adolescente , Adulto , Anciano , China/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad , Esputo , Adulto Joven
3.
Cochrane Database Syst Rev ; 1: CD012768, 2021 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-33448348

RESUMEN

BACKGROUND: Xpert MTB/RIF Ultra (Xpert Ultra) and Xpert MTB/RIF are World Health Organization (WHO)-recommended rapid nucleic acid amplification tests (NAATs) widely used for simultaneous detection of Mycobacterium tuberculosis complex and rifampicin resistance in sputum. To extend our previous review on extrapulmonary tuberculosis (Kohli 2018), we performed this update to inform updated WHO policy (WHO Consolidated Guidelines (Module 3) 2020). OBJECTIVES: To estimate diagnostic accuracy of Xpert Ultra and Xpert MTB/RIF for extrapulmonary tuberculosis and rifampicin resistance in adults with presumptive extrapulmonary tuberculosis. SEARCH METHODS: Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, Web of Science, Latin American Caribbean Health Sciences Literature, Scopus, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, the International Standard Randomized Controlled Trial Number Registry, and ProQuest, 2 August 2019 and 28 January 2020 (Xpert Ultra studies), without language restriction. SELECTION CRITERIA: Cross-sectional and cohort studies using non-respiratory specimens. Forms of extrapulmonary tuberculosis: tuberculous meningitis and pleural, lymph node, bone or joint, genitourinary, peritoneal, pericardial, disseminated tuberculosis. Reference standards were culture and a study-defined composite reference standard (tuberculosis detection); phenotypic drug susceptibility testing and line probe assays (rifampicin resistance detection). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias and applicability using QUADAS-2. For tuberculosis detection, we performed separate analyses by specimen type and reference standard using the bivariate model to estimate pooled sensitivity and specificity with 95% credible intervals (CrIs). We applied a latent class meta-analysis model to three forms of extrapulmonary tuberculosis. We assessed certainty of evidence using GRADE. MAIN RESULTS: 69 studies: 67 evaluated Xpert MTB/RIF and 11 evaluated Xpert Ultra, of which nine evaluated both tests. Most studies were conducted in China, India, South Africa, and Uganda. Overall, risk of bias was low for patient selection, index test, and flow and timing domains, and low (49%) or unclear (43%) for the reference standard domain. Applicability for the patient selection domain was unclear for most studies because we were unsure of the clinical settings. Cerebrospinal fluid Xpert Ultra (6 studies) Xpert Ultra pooled sensitivity and specificity (95% CrI) against culture were 89.4% (79.1 to 95.6) (89 participants; low-certainty evidence) and 91.2% (83.2 to 95.7) (386 participants; moderate-certainty evidence). Of 1000 people where 100 have tuberculous meningitis, 168 would be Xpert Ultra-positive: of these, 79 (47%) would not have tuberculosis (false-positives) and 832 would be Xpert Ultra-negative: of these, 11 (1%) would have tuberculosis (false-negatives). Xpert MTB/RIF (30 studies) Xpert MTB/RIF pooled sensitivity and specificity against culture were 71.1% (62.8 to 79.1) (571 participants; moderate-certainty evidence) and 96.9% (95.4 to 98.0) (2824 participants; high-certainty evidence). Of 1000 people where 100 have tuberculous meningitis, 99 would be Xpert MTB/RIF-positive: of these, 28 (28%) would not have tuberculosis; and 901 would be Xpert MTB/RIF-negative: of these, 29 (3%) would have tuberculosis. Pleural fluid Xpert Ultra (4 studies) Xpert Ultra pooled sensitivity and specificity against culture were 75.0% (58.0 to 86.4) (158 participants; very low-certainty evidence) and 87.0% (63.1 to 97.9) (240 participants; very low-certainty evidence). Of 1000 people where 100 have pleural tuberculosis, 192 would be Xpert Ultra-positive: of these, 117 (61%) would not have tuberculosis; and 808 would be Xpert Ultra-negative: of these, 25 (3%) would have tuberculosis. Xpert MTB/RIF (25 studies) Xpert MTB/RIF pooled sensitivity and specificity against culture were 49.5% (39.8 to 59.9) (644 participants; low-certainty evidence) and 98.9% (97.6 to 99.7) (2421 participants; high-certainty evidence). Of 1000 people where 100 have pleural tuberculosis, 60 would be Xpert MTB/RIF-positive: of these, 10 (17%) would not have tuberculosis; and 940 would be Xpert MTB/RIF-negative: of these, 50 (5%) would have tuberculosis. Lymph node aspirate Xpert Ultra (1 study) Xpert Ultra sensitivity and specificity (95% confidence interval) against composite reference standard were 70% (51 to 85) (30 participants; very low-certainty evidence) and 100% (92 to 100) (43 participants; low-certainty evidence). Of 1000 people where 100 have lymph node tuberculosis, 70 would be Xpert Ultra-positive and 0 (0%) would not have tuberculosis; 930 would be Xpert Ultra-negative and 30 (3%) would have tuberculosis. Xpert MTB/RIF (4 studies) Xpert MTB/RIF pooled sensitivity and specificity against composite reference standard were 81.6% (61.9 to 93.3) (377 participants; low-certainty evidence) and 96.4% (91.3 to 98.6) (302 participants; low-certainty evidence). Of 1000 people where 100 have lymph node tuberculosis, 118 would be Xpert MTB/RIF-positive and 37 (31%) would not have tuberculosis; 882 would be Xpert MTB/RIF-negative and 19 (2%) would have tuberculosis. In lymph node aspirate, Xpert MTB/RIF pooled specificity against culture was 86.2% (78.0 to 92.3), lower than that against a composite reference standard. Using the latent class model, Xpert MTB/RIF pooled specificity was 99.5% (99.1 to 99.7), similar to that observed with a composite reference standard. Rifampicin resistance Xpert Ultra (4 studies) Xpert Ultra pooled sensitivity and specificity were 100.0% (95.1 to 100.0), (24 participants; low-certainty evidence) and 100.0% (99.0 to 100.0) (105 participants; moderate-certainty evidence). Of 1000 people where 100 have rifampicin resistance, 100 would be Xpert Ultra-positive (resistant): of these, zero (0%) would not have rifampicin resistance; and 900 would be Xpert Ultra-negative (susceptible): of these, zero (0%) would have rifampicin resistance. Xpert MTB/RIF (19 studies) Xpert MTB/RIF pooled sensitivity and specificity were 96.5% (91.9 to 98.8) (148 participants; high-certainty evidence) and 99.1% (98.0 to 99.7) (822 participants; high-certainty evidence). Of 1000 people where 100 have rifampicin resistance, 105 would be Xpert MTB/RIF-positive (resistant): of these, 8 (8%) would not have rifampicin resistance; and 895 would be Xpert MTB/RIF-negative (susceptible): of these, 3 (0.3%) would have rifampicin resistance. AUTHORS' CONCLUSIONS: Xpert Ultra and Xpert MTB/RIF may be helpful in diagnosing extrapulmonary tuberculosis. Sensitivity varies across different extrapulmonary specimens: while for most specimens specificity is high, the tests rarely yield a positive result for people without tuberculosis. For tuberculous meningitis, Xpert Ultra had higher sensitivity and lower specificity than Xpert MTB/RIF against culture. Xpert Ultra and Xpert MTB/RIF had similar sensitivity and specificity for rifampicin resistance. Future research should acknowledge the concern associated with culture as a reference standard in paucibacillary specimens and consider ways to address this limitation.


Asunto(s)
Antibióticos Antituberculosos/uso terapéutico , Farmacorresistencia Bacteriana , Mycobacterium tuberculosis/efectos de los fármacos , Técnicas de Amplificación de Ácido Nucleico , Rifampin/uso terapéutico , Tuberculosis/diagnóstico , Adulto , Sesgo , Reacciones Falso Negativas , Reacciones Falso Positivas , Humanos , Mycobacterium tuberculosis/aislamiento & purificación , Técnicas de Amplificación de Ácido Nucleico/métodos , Técnicas de Amplificación de Ácido Nucleico/estadística & datos numéricos , Juego de Reactivos para Diagnóstico , Sensibilidad y Especificidad , Tuberculosis/líquido cefalorraquídeo , Tuberculosis/tratamiento farmacológico , Tuberculosis Ganglionar/líquido cefalorraquídeo , Tuberculosis Ganglionar/diagnóstico , Tuberculosis Ganglionar/tratamiento farmacológico , Tuberculosis Meníngea/líquido cefalorraquídeo , Tuberculosis Meníngea/diagnóstico , Tuberculosis Meníngea/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/líquido cefalorraquídeo , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Pleural/líquido cefalorraquídeo , Tuberculosis Pleural/diagnóstico , Tuberculosis Pleural/tratamiento farmacológico
4.
BMC Infect Dis ; 21(1): 123, 2021 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-33509114

RESUMEN

BACKGROUND: Xpert MTB/RIF (Xpert) has been recommended by WHO as the initial diagnostic test for TB and rifampicin-resistance detection. Existing evidence regarding its uptake is limited to public health systems and corresponding resource and infrastructure challenges. It cannot be readily extended to private providers, who treat more than half of India's TB cases and demonstrate complex diagnostic behavior. METHODS: We used routine program data collected from November 2014 to April 2017 from large-scale private sector engagement pilots in Mumbai and Patna. It included diagnostic vouchers issued to approximately 150,000 patients by about 1400 providers, aggregated to 18,890 provider-month observations. We constructed three metrics to capture provider behavior with regards to adoption of Xpert and studied their longitudinal variation: (i) Uptake (ordering of test), (ii) Utilization for TB diagnosis, and (iii) Non-adherence to negative results. We estimated multivariate linear regression models to assess heterogeneity in provider behavior based on providers' prior experience and Xpert testing volumes. RESULTS: Uptake of Xpert increased considerably in both Mumbai (from 36 to 60.4%) and Patna (from 12.2 to 45.1%). However, utilization of Xpert for TB diagnosis and non-adherence to negative Xpert results did not show systematic trends over time. In regression models, cumulative number of Xpert tests ordered was significantly associated with Xpert uptake in Patna and utilization for diagnosis in Mumbai (p-value< 0.01). Uptake of Xpert and its utilization for diagnosis was predicted to be higher in high-volume providers compared to low-volume providers and this gap was predicted to widen over time. CONCLUSIONS: Private sector engagement led to substantial increase in uptake of Xpert, especially among high-volume providers, but did not show strong evidence of Xpert results being integrated with TB diagnosis. Increasing availability and affordability of a technically superior diagnostic tool may not be sufficient to fundamentally change diagnosis and treatment of TB in the private sector. Behavioral interventions, specifically aimed at, integrating Xpert results into clinical decision making of private providers may be required to impact patient-level outcomes.


Asunto(s)
Técnicas de Diagnóstico Molecular/estadística & datos numéricos , Mycobacterium tuberculosis/aislamiento & purificación , Sector Privado/estadística & datos numéricos , Tuberculosis/diagnóstico , Antibióticos Antituberculosos/uso terapéutico , Farmacorresistencia Bacteriana/genética , Humanos , India/epidemiología , Mycobacterium tuberculosis/genética , Proyectos Piloto , Pautas de la Práctica en Medicina/estadística & datos numéricos , Rifampin/uso terapéutico , Tuberculosis/tratamiento farmacológico
5.
BMJ Case Rep ; 14(1)2021 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-33462021

RESUMEN

We present two unusual presentations of extrapulmonary tuberculosis (EPTB) and more specifically intra-abdominal tuberculosis (TB). These cases were initially suspicious for ovarian cancer, presenting with non-specific symptoms, ultrasound-confirmed ascites and elevated cancer antigen 125 tumour marker (CA 125). However, in both cases chest imaging demonstrated enlarged mediastinal nodes amenable to endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), which confirmed the diagnosis of TB. Both cases were successfully treated with quadruple TB therapy.


Asunto(s)
Dolor Abdominal/etiología , Antígeno Ca-125/sangre , Tuberculosis/diagnóstico , Adolescente , Biomarcadores/sangre , Nalgas , Femenino , Humanos , Persona de Mediana Edad , Tuberculosis/sangre , Tuberculosis/complicaciones
6.
Pathologe ; 42(1): 78-82, 2021 Feb.
Artículo en Alemán | MEDLINE | ID: mdl-33475809

RESUMEN

In the diagnosis of mycobacterioses, microbiological examination with culture and antibiogram, possibly in combination with molecular biological testing of the fresh material, still represents the gold standard. However, these methods are not available for formalin-fixed paraffin-embedded (FFPE) material or other fixed samples. For this reason, the first step in pathology is to attempt microscopic pathogen detection (ZN/Fite/rhodamine-auramine). Subsequently, molecular pathological examination for the detection of mycobacterial gene sequences should also be considered mandatory today. Although this has clear limits due to the material, it is nevertheless well suited, if carried out correctly, to detect a mycobacterial infection or make it unlikely. A negative result may favor an alternative diagnosis but does not completely rule out mycobacteriosis.For the therapy of tuberculosis or nontuberculous mycobacterial (NTM) disease, the reliable detection of the species and the determination of resistance is of utmost importance. With regard to therapy, the clinician cannot afford to make a false diagnosis. In case of doubt, a rebiopsy for sampling native material, particularly for microbiological testing, should be discussed.


Asunto(s)
Mycobacterium tuberculosis , Mycobacterium , Tuberculosis , ADN Bacteriano/genética , Humanos , Mycobacterium/genética , Mycobacterium tuberculosis/genética , Adhesión en Parafina , Patología Molecular , Reacción en Cadena de la Polimerasa , Tuberculosis/diagnóstico , Tuberculosis/genética
7.
Pathologe ; 42(1): 71-77, 2021 Feb.
Artículo en Alemán | MEDLINE | ID: mdl-33475810

RESUMEN

Although typical histological findings of tuberculosis are well known, the diagnosis of nonmicrobiologically proven tuberculosis with the instruments available to pathology is challenging. Indeed, necrotizing epithelioid cell granulomatosis is typical for tuberculosis, but it is also seen in a number of different infectious or noninfectious lung diseases. The tools of microscopy and molecular pathology are suitable for confirming the diagnosis or paving the way to a differential diagnosis, but molecular pathology applied to formalin-fixated and paraffin-embedded material is limited. This should be openly communicated to the referring clinician. After interdisciplinary re-evaluation of the findings, an alternative solution to confirm the diagnosis must therefore be found if the additional examinations are negative.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Pulmonar , Tuberculosis , Diagnóstico Diferencial , Formaldehído , Humanos , Pulmón , Adhesión en Parafina , Tuberculosis/diagnóstico , Tuberculosis Pulmonar/diagnóstico
8.
BMC Infect Dis ; 21(1): 106, 2021 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-33482742

RESUMEN

BACKGROUND: Gene expression signatures have been used as biomarkers of tuberculosis (TB) risk and outcomes. Platforms are needed to simplify access to these signatures and determine their validity in the setting of comorbidities. We developed a computational profiling platform of TB signature gene sets and characterized the diagnostic ability of existing signature gene sets to differentiate active TB from LTBI in the setting of malnutrition. METHODS: We curated 45 existing TB-related signature gene sets and developed our TBSignatureProfiler software toolkit that estimates gene set activity using multiple enrichment methods and allows visualization of single- and multi-pathway results. The TBSignatureProfiler software is available through Bioconductor and on GitHub. For evaluation in malnutrition, we used whole blood gene expression profiling from 23 severely malnourished Indian individuals with TB and 15 severely malnourished household contacts with latent TB infection (LTBI). Severe malnutrition was defined as body mass index (BMI) < 16 kg/m2 in adults and based on weight-for-height Z scores in children < 18 years. Gene expression was measured using RNA-sequencing. RESULTS: The comparison and visualization functions from the TBSignatureProfiler showed that TB gene sets performed well in malnourished individuals; 40 gene sets had statistically significant discriminative power for differentiating TB from LTBI, with area under the curve ranging from 0.662-0.989. Three gene sets were not significantly predictive. CONCLUSION: Our TBSignatureProfiler is a highly effective and user-friendly platform for applying and comparing published TB signature gene sets. Using this platform, we found that existing gene sets for TB function effectively in the setting of malnutrition, although differences in gene set applicability exist. RNA-sequencing gene sets should consider comorbidities and potential effects on diagnostic performance.


Asunto(s)
Perfilación de la Expresión Génica/métodos , Desnutrición/genética , Programas Informáticos , Tuberculosis/genética , Adolescente , Adulto , Anciano , Área Bajo la Curva , Biomarcadores/sangre , Niño , Comorbilidad , Femenino , Humanos , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/epidemiología , Tuberculosis Latente/genética , Masculino , Desnutrición/diagnóstico , Desnutrición/epidemiología , Persona de Mediana Edad , Mycobacterium tuberculosis , Transcriptoma , Tuberculosis/diagnóstico , Tuberculosis/epidemiología , Adulto Joven
9.
Z Gastroenterol ; 59(1): 50-55, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33429450

RESUMEN

Infections caused by pathogens of the Mycobacterium tuberculosis complex, i. e., tuberculosis (TB), and the non-infectious, autoimmune disease sarcoidosis are among the most common granulomatous diseases worldwide. Typically, the lung is the primary site of infection and manifestation, respectively which makes the two diseases important differential diagnoses. Both diseases can affect virtually all organ systems, albeit with significantly lower incidence. CASE PRESENTATION: We report the case of a 50-year-old Indian man presenting with a tuberculous perihepatic abscess and a systemic inflammatory response after being diagnosed with neurosarcoidosis presenting as a single granuloma in the frontal lobe with lymphadenopathy in 2014. On day of admission the patient presented with right upper abdominal pain and fever for two weeks. With increased inflammatory parameters in serum and after finding of external CT images, a perihepatic abscess was suspected. This encapsulated cave was drained percutaneously under CT control. A high concentration of acid-fast rods was detected using ZN, PCR was positive for M. tuberculosis. Several samples of sputum and urine were microscopically negative but yielded growth of Mycobacteria after four weeks. DISCUSSION: This is a case presenting with two different granulomatous diseases, each of which manifested itself in an atypical form. The tuberculous liver abscess might either be explained as a flare-up of latent tuberculosis under azathioprine therapy or as a reinfection acquired during one of several visits in the high-prevalence country India. In addition, it must be discussed whether the cerebral granuloma in 2014 could have been an early stage of tuberculous granuloma. Sensitivity of ZN staining is significantly reduced in cerebral samples, and negative PCR-results might be due to low germ load or methodical issues, e. g., decreased sensitivity in formalin fixated samples.


Asunto(s)
Enfermedades del Sistema Nervioso Central/diagnóstico , Mycobacterium tuberculosis/aislamiento & purificación , Sarcoidosis/diagnóstico , Tuberculosis/diagnóstico , Dolor Abdominal/etiología , Drenaje , Fiebre/etiología , Granuloma/diagnóstico , Humanos , Absceso Hepático/microbiología , Absceso Hepático/cirugía , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/genética , Reacción en Cadena de la Polimerasa , Resultado del Tratamiento , Tuberculosis/tratamiento farmacológico
10.
Respir Res ; 22(1): 23, 2021 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-33472618

RESUMEN

BACKGROUND: When infected with Mycobacterium tuberculosis, only a small proportion of the population will develop active TB, and the role of host genetic factors in different TB infection status was not fully understood. METHODS: Forty-three patients with active tuberculosis and 49 with latent tuberculosis were enrolled in the prospective cohort. Expressing levels of 27 candidate mRNAs, which were previously demonstrated to differentially expressed in latent and active TB, were measured by dual color reverse transcription multiplex ligation dependent probe amplification assay (dcRT-MLPA). Using expression levels of these mRNAs as quantitative traits, associations between expression abundance and genome-wild single nucleotide polymorphisms (SNPs) were calculated. Finally, identified candidate SNPs were further assessed for their associations with TB infection status in a validation cohort with 313 Chinese Han cases. RESULTS: We identified 9 differentially expressed mRNAs including il7r, il4, il8, tnfrsf1b, pgm5, ccl19, il2ra, marco and fpr1 in the prospective cohort. Through expression quantitative trait loci mapping, we screened out 8 SNPs associated with these mRNAs. Then, CG genotype of the SNP rs62292160 was finally verified to be significantly associated with higher transcription levels of IL4 in LTBI than in TB patients. CONCLUSION: We reported that the SNP rs62292160 in Chinese Han population may link to higher expression of il4 in latent tuberculosis. Our findings provided a new genetic variation locus for further exploration of the mechanisms of TB and a possible target for TB genetic susceptibility studies, which might aid the clinical decision to precision treatment of TB.


Asunto(s)
Grupo de Ascendencia Continental Asiática/genética , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo/métodos , Sitios de Carácter Cuantitativo/genética , ADN Polimerasa Dirigida por ARN/genética , Tuberculosis/genética , Adulto , China/epidemiología , Estudios de Cohortes , Femenino , Expresión Génica , Redes Reguladoras de Genes/genética , Predisposición Genética a la Enfermedad/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Estudios Prospectivos , Tuberculosis/diagnóstico , Tuberculosis/epidemiología
11.
West Afr J Med ; 38(1): 1-2, 2021 01.
Artículo en Inglés, Francés | MEDLINE | ID: mdl-33463698

RESUMEN

EDITORIAL.


Asunto(s)
Tuberculosis , Humanos , Tuberculosis/diagnóstico
12.
Medicine (Baltimore) ; 99(52): e23775, 2020 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-33350763

RESUMEN

ABSTRACT: Nontuberculous mycobacteria (NTM) infection may interfere in the diagnosis and treatment of tuberculosis (TB) in TB-endemic regions. However, the population-based incidence of NTM disease and NTM-TB coinfection remains unclear.We used Taiwan's National Health Insurance Research Database to identify new diagnoses of NTM disease and TB from 2005 to 2013 and calculated the incidence rate and the proportion of NTM-TB coinfection. The patients with NTM disease or TB were determined by the use of disease codes from International Classification of Diseases, Ninth Revision, Clinical Modification, laboratory mycobacterium examination codes, and antimycobacterial therapy receipts.From 2005 to 2013, the age-adjusted incidence rate of NTM disease increased from 5.3 to 14.8 per 100,000 people per year and the age-adjusted incidence rate of NTM-TB coinfection was around 1.2 to 2.2 per 100,000 people per year. The proportion of NTM-TB coinfection among patients with confirmed TB was 2.8%. Male and older patients had a significantly higher incidence of NTM disease. The effects of urbanization and socioeconomic status (SES) on the incidences of TB and NTM disease were different. Rural living and lower SES were significantly associated with increasing the incidence of confirmed TB but not with that of NTM disease. For NTM disease, those living in the least urbanized area had significantly lower incidence rate ratio than in the highest urbanized area. The incidence of NTM-TB coinfection was higher in older patients and compared with patients aged < 45 years, the incidence rate ratio of the patients aged> 74 years was 12.5.In TB-endemic Taiwan, the incidence of NTM disease increased from 2005 to 2013. Male gender and old age were risk factors for high incidence of NTM disease. SES did not have a significant effect on the incidence of NTM disease, but rural living was associated with lower incidence of NTM disease. In TB-endemic areas, NTM-TB coinfection could disturb the diagnosis of TB and treatment, especially in elderly patients.


Asunto(s)
Coinfección/epidemiología , Infecciones por Mycobacterium no Tuberculosas , Tuberculosis , Adulto , Factores de Edad , Anciano , Estudios de Cohortes , Enfermedades Endémicas/estadística & datos numéricos , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Factores Socioeconómicos , Taiwán/epidemiología , Tuberculosis/diagnóstico , Tuberculosis/epidemiología
13.
BMJ Case Rep ; 13(12)2020 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-33310826

RESUMEN

Tuberculosis (TB) of the breast is extremely rare and is often mistaken for benign or malignant lesions of the breast. They are rare even in countries which are endemic for TB, like India. The most common type of clinical presentation is a vague lump in the breast, but there are even other types of presentations which are documented. In olden days, there was a lot of dilemma and challenge in diagnosing TB of the breast, but thanks to improved pathological knowledge and the advent of investigations such as QuantiFERON-TB gold and GeneXpert, TB can be diagnosed early nowadays and treated accordingly. In this study series, we report 10 cases of TB of the breast with variable clinical presentations as fibroadenosis, breast abscess, duct ectasia and breast lump on evaluation, and the challenges encountered in establishing the diagnosis.


Asunto(s)
Enfermedades de la Mama/diagnóstico , Mama/microbiología , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis/diagnóstico , Adulto , Mama/patología , Enfermedades de la Mama/fisiopatología , ADN Bacteriano/análisis , Diagnóstico Diferencial , Femenino , Humanos , India , Persona de Mediana Edad , Estudios Retrospectivos
14.
J Med Chem ; 63(24): 15308-15332, 2020 12 24.
Artículo en Inglés | MEDLINE | ID: mdl-33307693

RESUMEN

Tuberculosis (TB) remains one of the deadliest infectious diseases and begs the scientific community to up the ante for research and exploration of completely novel therapeutic avenues. Chemical biology-inspired design of tunable chemical tools has aided in clinical diagnosis, facilitated discovery of therapeutics, and begun to enable investigation of virulence mechanisms at the host-pathogen interface of Mycobacterium tuberculosis. This Perspective highlights chemical tools specific to mycobacterial proteins and the cell lipid envelope that have furnished rapid and selective diagnostic strategies and provided unprecedented insights into the function of the mycobacterial proteome and lipidome. We discuss chemical tools that have enabled elucidating otherwise intractable biological processes by leveraging the unique lipid and metabolite repertoire of mycobacterial species. Some of these probes represent exciting starting points with the potential to illuminate poorly understood aspects of mycobacterial pathogenesis, particularly the host membrane-pathogen interactions.


Asunto(s)
Mycobacterium tuberculosis/metabolismo , Tuberculosis/diagnóstico , Oxidorreductasas de Alcohol/química , Oxidorreductasas de Alcohol/metabolismo , Animales , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Pared Celular/metabolismo , Colorantes Fluorescentes/química , Humanos , Lípidos/química , Sondas Moleculares/química , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/patogenicidad , Peptidoglicano/química , Sulfatasas/química , Sulfatasas/metabolismo , Trehalosa/química , Tuberculosis/microbiología , Virulencia/genética
15.
PLoS One ; 15(12): e0243765, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33315919

RESUMEN

BACKGROUND: Abdominal tuberculosis is a severe extrapulmonary tuberculosis, which can lead to serious complications. Early diagnosis and treatment are very important for the prognosis and the diagnosis of abdominal tuberculosis is still difficult. This study aims to evaluate the diagnostic accuracy of nucleic acid amplification tests (NAATs) for abdominal tuberculosis using meta-analysis method. METHODS: We will search PubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure, and the Wanfang database for studies evaluating the diagnostic accuracy of NAATs for abdominal tuberculosis until May 2020. We will include a systematic review and meta-analysis that evaluated the accuracy of NAATs for abdominal tuberculosis. Any types of study design with full text will be sought and included. The risk of bias will be assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. Stata version 15.0 with the midas command packages will be used to carry out meta-analyses. RESULTS: The results will provide clinical evidence for diagnostic accuracy of NAATs for abdominal tuberculosis, and this systematic review and meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This overview will provide evidence of NAATs for diagnosis of abdominal tuberculosis. SYSTEMATIC REVIEW REGISTRATION: INPLASY202060030.


Asunto(s)
Técnicas de Amplificación de Ácido Nucleico/métodos , Tuberculosis/diagnóstico , Abdomen/microbiología , ADN Bacteriano/análisis , ADN Bacteriano/metabolismo , ADN Bacteriano/normas , Bases de Datos Factuales , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Estándares de Referencia , Tuberculosis/microbiología
16.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(12): 1300-1305, 2020 Dec.
Artículo en Chino | MEDLINE | ID: mdl-33328001

RESUMEN

OBJECTIVE: To study the clinical features of Mycobacterium tuberculosis infection in children with secondary immunodeficiency disease (SID) versus primary immunodeficiency disease (PID). METHODS: A retrospective analysis was performed on the medical data of children with immunodeficiency and Mycobacterium tuberculosis infection (36 children with SID and 52 with PID) and 108 children with Mycobacterium tuberculosis infection but without immunodeficiency (control group). RESULTS: The onset age in the PID group was significantly lower than those in the control and SID groups (P < 0.05), and the proportation of males in the PID group was significantly higher than those in the control and SID groups (P < 0.05). Compared with the control group, the SID and PID groups had significantly lower incidence rates of tuberculosis poisoning symptoms (night sweeting, weight loss, fatigue and loss of appetite) and positive rate of PPD test (P < 0.05), as well as a significantly higher incidence rate of the involvement of ≥ 3 pulmonary lobes (P < 0.05). The children with PID tended to have the involvement of multiple organs (P < 0.05). The SID group had a significantly higher incidence rate of miliary shadow on chest CT than the control and PID groups (P < 0.05). The PID group had a significantly lower positive rate of IFN-gamma release assay (IGRA) than the control and SID groups (P < 0.05). Mycobacterium tuberculosis infection manifested as latent tuberculosis infection (36.1%) and active tuberculosis (63.9%) in the SID group. The infection mainly manifested as bacille Calmette-Guérin disease in the PID group (90.4%), among whom 2 children (3.8%) also had tuberculosis. CONCLUSIONS: Children with immunodeficiency and Mycobacterium tuberculosis infection have atypical clinical symptoms, with a high incidence rate of disseminated infection and low positive rates of PPD and IGRA tests, which may lead to misdiagnosis and missed diagnosis. Children with immunodeficiency should undergo regular tuberculosis screening for early identification and intervention.


Asunto(s)
Síndromes de Inmunodeficiencia , Tuberculosis , Edad de Inicio , Niño , Humanos , Síndromes de Inmunodeficiencia/complicaciones , Síndromes de Inmunodeficiencia/diagnóstico , Masculino , Estudios Retrospectivos , Prueba de Tuberculina , Tuberculosis/diagnóstico , Tuberculosis/epidemiología
17.
PLoS One ; 15(12): e0243610, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33315902

RESUMEN

Surveillance is critical for interrupting transmission of global epidemics. Research has highlighted gaps in the surveillance for tuberculosis that range from failure to collect real-time data to lack of standardization of data for informed decision-making at different levels of the health system. Our research aims to advance conceptual and methodological foundations for the development of a learning surveillance system for Tuberculosis, that involves systematic collection, analysis, interpretation, and feedback of outcome-specific data. It would concurrently involve the health care delivery system, public health laboratory, and epidemiologists. For our study, we systemically framed the cyber environment of TB surveillance as an ontology of the learning surveillance system. We validated the ontology by binary coding of dimensions and elements of the ontology with the metadata from an existing surveillance platform-GPMS TB Transportal. Results show GPMS TB Transportal collects a critical range of data for active case investigation and presumptive case screening for identifying and detecting confirmed TB cases. It is therefore targeted at assisting the Active Case Finding program. Building on the results, we demonstrate enhanced surveillance strategies for GPMS that are enumerated as pathways in the ontology. Our analysis reveals the scope for embedding learning surveillance pathways for digital applications in Direct Benefit Transfer, and Drug Resistance Treatment in National TB Elimination Programme in India. We discuss the possibilities of developing the transportal into a multi-level computer-aided decision support system for TB, using the innumerable pathways encapsulated in the ontology.


Asunto(s)
Vigilancia en Salud Pública , Tuberculosis/epidemiología , Ontologías Biológicas , Humanos , India/epidemiología , Tamizaje Masivo , Salud Pública , Tuberculosis/diagnóstico
18.
Indian J Tuberc ; 67(4S): S101-S106, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33308653

RESUMEN

Case finding, an important parameter in fight against Tuberculosis (TB) has always remained a challenge despite advances in diagnostic modalities, access to health care and administrative commitment. We are still far from reaching the goals so set as per End TB Strategy and National Strategic Plan 2017-2025, and case finding is of paramount importance for achieving the said targets. This article, after identifying the obstacles faced in case finding, explores the various case finding strategies in the perspective of diagnostics, feasibility, resource utilization and current recommendations. Need for prioritization of case finding in different settings with involvement and active participation of one and all has been discussed. Role of health education in an individual, general public and health care worker in the context of case finding has been highlighted. Research areas to strengthen case finding have been enumerated. The review concludes by bringing out the need for heightened efforts for case finding in TB as the resources are significantly diverted as the world is facing the corona virus disease 2019 (COVID-19) pandemic.


Asunto(s)
/epidemiología , Tamizaje Masivo/organización & administración , Tuberculosis/diagnóstico , Humanos , Planificación Estratégica , Tuberculosis/terapia
19.
Indian J Tuberc ; 67(4S): S139-S146, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33308660

RESUMEN

India has the highest burden of incident tuberculosis (TB) cases and deaths globally. TB is strongly associated with poverty and this risk is largely mediated by undernutrition in India. COVID-19 response related lockdown has resulted in an economic crisis which may double levels of poverty, has exacerbated food insecurity, and disrupted TB services. These developments may have serious implications for TB progression and transmission in India. The nutritional status of a population is a strong determinant of the TB incidence, and undernutrition in adults alone accounts for 32-44% of TB incidence in India. A systematic review has shown that a 14% increase in TB incidence can occur per one unit decrease in body mass index (BMI), across the BMI range of 18.5-30 kg/m2. We believe that one unit decrease in BMI (corresponding to a 2-3 kg weight loss) may result in the poor in India as a result of the lockdown and its aftermath. This may result in an increase in estimated (uncertainty interval) incident TB by 185 610 (180 230, 190 990) cases. A 59% reduction in TB case detection between end March and May 2020, may result in an estimated (uncertainty interval) additional 87 711 (59 998, 120 630) TB deaths [19.5% increase (14.5, 24.7)] in 2020. Disadvantaged social groups and those living in states with higher levels of poverty, under-nutrition,and migrant workers are at particular risk. We suggest enhanced rations including pulses through the public distribution system and direct cash transfers to the poor pending restoration of livelihoods. TB services should be resumed immediately with enhanced efforts at case detection including active case finding. To prevent deaths among TB detected within the national TB programme, systemic identification, referral and management of severe disease at notification should be considered.


Asunto(s)
/prevención & control , Control de Enfermedades Transmisibles , Accesibilidad a los Servicios de Salud , Tuberculosis/epidemiología , Adulto , /transmisión , Humanos , Incidencia , India/epidemiología , Estado Nutricional , Tuberculosis/diagnóstico , Tuberculosis/terapia
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