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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
BACKGROUND: Tuberculosis (TB) is caused due to the infection of Mycobacterium tuberculosis (MTB) and it can infect the various parts of the human body. The disease is highly prevalent and is the second most common cause of death worldwide after COVID-19. Apart from sputum specimen, it is exceedingly difficult to diagnose due to its paucibacillary nature. The current study was intended to evaluate the accuracy of Smart Sure™ MTB and multidrug-resistant-TB (MDR-TB) kits (Genetix Biotech Asia Pvt. Ltd., India) with Xpert ultra and Mycobacterium growth indicator tube (MGIT) culture on nonsputum specimens from TB suspects. METHODS: A total of 205 nonsputum specimens were received between October 2023 and May 2024 at Intermediate Reference Laboratory, Department of Medicine, All India Institute of Medical Sciences, New Delhi, India. Xpert ultra and Smart Sure™ MTB and MDR-TB tests were done directly on samples. However, processed specimens were used for MGIT culture and drug-susceptibility testing (DST). Invalid and MGIT contaminated specimens were excluded from the final calculation. RESULTS: Overall, sensitivity and specificity of Smart Sure™ MTB screening kit was 71.59% and 98.28%, respectively, with Xpert ultra and 68.35% and 90.83%, respectively, with MGIT culture. While comparing with both Xpert ultra and MGIT-DST to detect rifampicin (RIF) resistant, Smart Sure™ MDR-TB kits showed sensitivity of 75.0% and 100% of specificity. However, for isoniazid (INH) resistance, Smart Sure™ MDR-TB kits showed 100% of sensitivity and specificity with MGIT-DST. CONCLUSION: For the detection of MTB and its drug-resistance patterns (RIF and INH) in the specimens other than sputum, Smart Sure™ MTB and MDR-TB kits could play a vital role in TB endemic countries. While comparing the set-ups and skilled staffs, it required almost same as compared with previously approved WHO diagnostics used in resource-limited countries.
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Mycobacterium tuberculosis , Juego de Reactivos para Diagnóstico , Sensibilidad y Especificidad , Centros de Atención Terciaria , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , India , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Pruebas de Sensibilidad Microbiana/instrumentación , Pruebas de Sensibilidad Microbiana/métodos , Esputo/microbiología , Antituberculosos/farmacología , Rifampin/farmacología , Isoniazida/farmacologíaRESUMEN
Lack of appropriate early diagnostic tools for drug-resistant tuberculosis (DR-TB) and their incomplete drug susceptibility testing (DST) profiling is concerning for TB disease control. Existing methods, such as phenotypic DST (pDST), are time-consuming, while Xpert MTB/RIF (Xpert) and line probe assay (LPA) are limited to detecting resistance to few drugs. Targeted next-generation sequencing (tNGS) has been recently approved by WHO as an alternative approach for rapid and comprehensive DST. We aimed to investigate the performance and feasibility of tNGS for detecting DR-TB directly from clinical samples in Bangladesh. pDST, LPA and tNGS were performed among 264 sputum samples, either rifampicin-resistant (RR) or rifampicin-sensitive (RS) TB cases confirmed by Xpert assay. Resistotypes of tNGS were compared with pDST, LPA and composite reference standard (CRS, resistant if either pDST or LPA showed a resistant result). tNGS results revealed higher sensitivities for rifampicin (RIF) (99.3%), isoniazid (INH) (96.3%), fluoroquinolones (FQs) (94.4%), and aminoglycosides (AMGs) (100%) but comparatively lower for ethambutol (76.6%), streptomycin (68.7%), ethionamide (56.0%) and pyrazinamide (50.7%) when compared with pDST. The sensitivities of tNGS for INH, RIF, FQs and AMGs were 93.0%, 96.6%, 90.9%, and 100%, respectively and the specificities ranged from 91.3 to 100% when compared with CRS. This proof of concept study, conducted in a high-burden setting demonstrated that tNGS is a valuable tool for identifying DR-TB directly from the clinical specimens. Its feasibility in our laboratory suggests potential implementation and moving tNGS from research settings into clinical settings.
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Antituberculosos , Secuenciación de Nucleótidos de Alto Rendimiento , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Bangladesh , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Antituberculosos/farmacología , Esputo/microbiología , Rifampin/farmacología , Masculino , Femenino , Adulto , Sensibilidad y Especificidad , Persona de Mediana Edad , Farmacorresistencia Bacteriana Múltiple/genéticaRESUMEN
Single-nucleotide polymorphism (SNP) detection is critical for diagnosing diseases, and the development of rapid and accurate diagnostic tools is essential for treatment and prevention. Allele-specific polymerase chain reaction (AS-PCR) is widely used for detecting SNPs with multiplexing capabilities, while CRISPR-based technologies provide high sensitivity and specificity in targeting mutation sites through specific guide RNAs (gRNAs). In this study, we have integrated the high sensitivity and specificity of CRISPR technology with the multiplexing capabilities of AS-PCR, achieving the simultaneous detection of ten single-base mutations. As for Multi-AS-PCR, our research identified that competitive inhibition of primers targeting the same loci, coupled with divergent amplification efficiencies of these primers, could result in diminished amplification efficiency. Consequently, we adjusted and optimized primer combinations and ratios to enhance the amplification efficacy of Multi-AS-PCR. Finally, we successfully developed a novel nested Multi-AS-PCR-Cas12a method for multiplex SNPs detection. To evaluate the clinical utility of this method in a real-world setting, we applied it to diagnose rifampicin-resistant tuberculosis (TB). The limit of detection (LoD) for the nested Multi-AS-PCR-Cas12a was 102 aM, achieving sensitivity, specificity, positive predictive value, and negative predictive value of 100 %, 93.33 %, 90.00 %, and 100 %, respectively, compared to sequencing. In summary, by employing an innovative design that incorporates a universal reverse primer alongside ten distinct forward allele-specific primers, the nested Multi-AS-PCR-Cas12a technique facilitates the parallel detection of ten rpoB gene SNPs. This method also holds broad potential for the detection of drug-resistant gene mutations in infectious diseases and tumors, as well as for the screening of specific genetic disorders.
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Sistemas CRISPR-Cas , Polimorfismo de Nucleótido Simple , Sistemas CRISPR-Cas/genética , Humanos , Reacción en Cadena de la Polimerasa/métodos , Mutación , Mycobacterium tuberculosis/genética , Rifampin/farmacología , Límite de Detección , Reacción en Cadena de la Polimerasa Multiplex/métodos , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/genética , Proteínas Bacterianas , Endodesoxirribonucleasas , Proteínas Asociadas a CRISPRRESUMEN
Objective: 1) To evaluate the contribution of the GeneXpert® MTB/RIF (GX) test in the diagnosis of pulmonary and extra-pulmonary tuberculosis compared to culture. 2) To compare the rifampicin results resistance obtained by GX with the phenotypic sensitivity test. Materials and methods: Retrospective study carried out over a period of five years, from May 2017 to June 2022 at the microbiology laboratory of the Central army Hospital Mohamed Seghir Nekkache, Algiers (Algeria). The pulmonary and extrapulmonary clinical specimens were collected, cultivated, tested by GX PCR and direct examination by Ziehl-Neelsen staining. The study of sensitivity to antituberculosis drugs was performed according to the proportion method on liquid medium Bactec MGIT 960 (or on solid medium Lowenstein-Jensen at the Algerian Pasteur Institute). Results: 310 samples were included in the final analysis of the study, of which 156 were of pulmonary origin and 154 of extrapulmonary origin. Mycobacterium tuberculosis complex (MTBC) was detected in 95 samples from 88 tuberculosis patients (sex ratio 2,03 and middle age 37 years) with 49 cases of pulmonary tuberculosis and 39 cases of extra-pulmonary tuberculosis. For 2 cases, the GX was positive while the culture was negative and for 11 cases, the GX was negative while the culture was positive. Thus, in our study and compared to culture, GX showed an overall sensitivity of 88.2%, a specificity of 98.6%, a positive predictive value (PPV) of 96.4% and a negative predictive value (NPV) of 95.2%. The analysis of the data according to the type of samples, the sensitivity, specificity, PPV and NPV of GX for the pulmonary and extrapulmonary samples were 96.3% vs. 77.0%, 98.0% vs. 99.1%, 96.2% vs. 96.5% and 98.0% vs. 92.7% respectively. The sensitivity of GX for disco-vertebral, lymph node, meningeal and pleural tuberculosis were 100%, 90.0%, 71.4% and 57.1% respectively. The sensitivity of GX for pulmonary tuberculosis compared to microscopy was 96% vs. 68%. The comparison of the results of detection of resistance to rifampicin by GX and by phenotypic methods showed perfect agreement. Discussion and conclusion: A good sensitivity of GX compared to microscopy was revealed. The GX is a useful tool for the diagnosis of pulmonary tuberculosis, especially in smear-negative cases. The sensitivity of GX in extrapulmonary tuberculosis varied depending on the location of the infection. A negative result by GX does not exclude tuberculosis and cases of resistance to RIF detected by GX must be confirmed by phenotypic method.
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Antibióticos Antituberculosos , Mycobacterium tuberculosis , Rifampin , Humanos , Argelia , Rifampin/farmacología , Estudios Retrospectivos , Femenino , Masculino , Adulto , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Persona de Mediana Edad , Antibióticos Antituberculosos/farmacología , Farmacorresistencia Bacteriana/genética , Adulto Joven , Tuberculosis/diagnóstico , Tuberculosis/microbiología , Tuberculosis/tratamiento farmacológico , Técnicas de Diagnóstico Molecular/métodos , Pruebas de Sensibilidad Microbiana , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiología , Anciano , Adolescente , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Sensibilidad y EspecificidadRESUMEN
This case report presents an atypical manifestation of tuberculosis in a 21-year-old male who presented with multiple subcutaneous swellings in the bilateral heel, left elbow, and base of the left third finger for the previous 6 months. The patient also experienced loss of appetite and unintentional weight loss. Despite initial suspicion of bacterial abscesses, antibiotics did not lead to significant improvement. Further investigations revealed an elevated erythrocyte sedimentation rate and findings suggestive of osteomyelitis on imaging. Gene Xpert testing confirmed multidrug-resistant Mycobacterium tuberculosis as the causative agent. The patient was prescribed a bedaquiline-based multidrug-resistant tuberculosis regimen, which resulted in reduction in swelling size. This report highlights the challenges in diagnosing and managing complex cases of primary multiple tubercular abscesses, especially with drug-resistant strains, emphasizing the importance of timely diagnosis and multidisciplinary management for successful outcomes.
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Absceso , Antituberculosos , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Masculino , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Adulto Joven , Absceso/microbiología , Absceso/tratamiento farmacológico , Antituberculosos/uso terapéutico , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificaciónRESUMEN
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Antituberculosos , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis , Sensibilidad y Especificidad , Esputo , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Estudios Prospectivos , Mycobacterium tuberculosis/aislamiento & purificación , Mycobacterium tuberculosis/efectos de los fármacos , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Esputo/microbiología , Antituberculosos/farmacología , Agar , Líquido del Lavado Bronquioalveolar/microbiología , Femenino , Adulto , Factores de Tiempo , Masculino , Derrame Pleural/microbiología , Derrame Pleural/diagnóstico , Medios de Cultivo , Persona de Mediana EdadRESUMEN
Tuberculosis is a preventable and generally curable infectious disease caused by Mycobacterium tuberculosis. It mostly affects the lungs causing pulmonary tuberculosis; however, it may also involve non-pulmonary organs resulting in extrapulmonary tuberculosis (EPTB). Diagnosis of tuberculosis was based on the constitutional symptoms, organ-specific radiographs, and biological specimen examination. However, diagnosis of extrapulmonary tuberculosis can be difficult when the lungs are not affected and constitutional signs and symptoms of tuberculosis that can help to identify the disease are absent. Although multi-drug-resistant extrapulmonary tuberculosis is not uncommon, primary drug-resistant extrapulmonary tuberculosis in certain areas such as the extraspinal osteoarticular joint, tympanic membrane, and central nervous system is still rare. In this piece, we present three cases of primary multidrug-resistant extrapulmonary tuberculosis with an unusual presentation.
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Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Masculino , Femenino , Adulto , Antituberculosos/uso terapéutico , Persona de Mediana Edad , Mycobacterium tuberculosis/aislamiento & purificación , Mycobacterium tuberculosis/efectos de los fármacos , Tuberculosis Osteoarticular/tratamiento farmacológico , Tuberculosis Osteoarticular/diagnóstico , Tuberculosis ExtrapulmonarRESUMEN
BACKGROUND: Currently for diagnosing Mycobacterium tuberculosis and its drug resistance, two sputum samples are required. One of them is subjected to TrueNat™ and if positive the other sample is subjected to line probe assay (LPA). This study was done to evaluate whether TrueNat extracted DNA can be directly used for performing LPA in a diagnostic laboratory setting to decrease patient turn-around time. METHODS: Total 45 smear positive sputum samples were subjected to TrueNat™ MTB detection and first and second line (FL and SL) LPA testing in parallel. DNA extracted by Trueprep® Cartridge was also tested by LPA and results were compared. Further, TrueNat extracted DNA from 20 samples was divided into 6 aliquots each, two of which were stored at 4 °C, 37 °C and 55 °C (under humidification) each. One aliquot from stored DNA at each temperature was used for FL & SL LPA on day three and the other on day eight. The blots thus obtained were compared with those of conventional LPA at day 1. RESULTS: For FL-LPA, TrueNat extracted DNA gave valid results for all 45 (100%) samples but conventionally extracted DNA could give results for 44 (97.8%) samples. Likewise, for SL-LPA, valid results were obtained for 40 (88.9%) and 35 (77.8%) samples respectively using TrueNat extracted DNA and conventionally extracted DNA respectively. All samples with invalid LPA results had Ct values ≥ 28 by TrueNat PCR. LPA results were obtained for all the 20 samples using stored DNA at all temperatures and duration. CONCLUSIONS: TrueNat extracted DNA can be used for performing LPA under field conditions for selected samples.
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ADN Bacteriano , Mycobacterium tuberculosis , Esputo , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , ADN Bacteriano/análisis , Esputo/microbiología , Tuberculosis Pulmonar/diagnóstico , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Pericardial effusion is the accumulation of fluid in the pericardial cavity. In nations with high tuberculosis (TB) load, TB is the most common cause of pericardial effusion. 1-2% of patients with pulmonary TB develop Pericardial TB worldwide. Multi-drug-resistant (MDR) TB, including extrapulmonary TB (EPTB) cases, are rising in number. Adenosine Deaminase (ADA) is an enzyme in lymphocytes and myeloid cells, which has certain immune functions in the body. ADA levels are increased in inflammatory conditions, like pleural, pericardial, or joint effusions, of bacterial etiology, granulomatous conditions, neoplasms, and autoimmune pathologies. TB is the only lymphocytosis involving disease with increased ADA levels. MDR EPTB is rare, but cases are on the rise, and tuberculous pericardial effusion is one such example. Hence, it is important to know the percentage of cases detected by a culture that can be identified by cartridge-based nucleic acid amplification test (CBNAAT), their resistance patterns, and to identify potential markers like ADA, which can help in early identification of cases. The objectives of this study were to identify the Mycobacterium tuberculosis (MTB) bacilli in culture, and correlate them with cartridge-based nucleic acid amplification test (CBNAAT) results and their drug-resistance, in the Pericardial tubercular effusion, and to find if Adenosine Deaminase (ADA) levels can be used as a predictor of the presence of MTB in pericardial fluid. METHODOLOGY: We enrolled 52 patients with moderate to large tuberculous pericardial effusion, based on pericardial fluid analysis, CBNAAT, and culture methods, between January 2021 and December 2021. RESULTS: The mean age of the patients was 41.85 + 17.88 years, with a median of 38 years. Males made up 57.7% of the total patients. MTB was detected in 16 (30.8%) patients in the CBNAAT evaluations. 14 (87.5%) of the CBNAAT-positive TB patients were sensitive to Rifampicin, whereas the remaining 2 (12.5%) were resistant to Rifampicin on CBNAAT. MTB was found to be growing in 8 (15.38%) drug sensitivity test cultures. Out of these 8, 6 were sensitive to first-line drugs, whereas 2 were resistant to both Isoniazid and Rifampicin. The presence of cough was found to have a significant difference between CBNAAT-detected MTB positive and negative patients (p = 0.020), whereas an insignificant difference was found for the presence of hypertension, diabetes mellitus, obesity, dyspnea, or fever. There was also an insignificant difference between the number of patients positive for the Tuberculin skin test, between the two groups. ADA was significantly higher in the MTB-detected CBNAAT group (85.91 + 37.60U/L vs 39.78 + 24.31U/L, p = 0.005), whereas the total leukocyte count, lymphocytes, neutrophils, random blood sugar levels, and serum protein levels had no significant difference. The area under the Receiver Operator Curve (CBNAAT positive: dependent variable; ADA: test result variable) was 0.854 (null hypothesis rejected), with a standard error of 0.078. CONCLUSIONS: Culture is the gold standard method to diagnose tuberculosis. Detection of MTB on pericardial fluid culture is very uncommon, though in our study, culture came out positive in 16% of patients, and 4% were resistant to rifampicin and isoniazid. Higher ADA levels in pericardial fluid are an indicator of tuberculous pericardial effusion.
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Adenosina Desaminasa , Mycobacterium tuberculosis , Técnicas de Amplificación de Ácido Nucleico , Derrame Pericárdico , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Adenosina Desaminasa/análisis , Adenosina Desaminasa/metabolismo , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Masculino , Adulto , Femenino , Derrame Pericárdico/microbiología , Persona de Mediana Edad , Líquido Pericárdico , Adulto Joven , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Pericarditis Tuberculosa/diagnósticoAsunto(s)
Tortícolis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Tortícolis/tratamiento farmacológico , Tortícolis/etiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Masculino , Antituberculosos/uso terapéutico , AdultoRESUMEN
Drug-resistant tuberculosis (TB) has poor outcomes unless resistance is detected early, ideally by commercially available molecular tests. We present a case of occult multidrug-resistant TB where both rifampicin and isoniazid resistance were missed by molecular testing and were only identified by phenotypic testing.
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Antituberculosos , Isoniazida , Mycobacterium tuberculosis , Rifampin , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Rifampin/farmacología , Rifampin/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Antituberculosos/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Masculino , AdultoRESUMEN
BACKGROUND: This study aims to explore the varied experiences of patients with drug-resistant tuberculosis in Norway. The study emphasizes challenges and implications of being diagnosed with drug-resistant tuberculosis, including the impact on psychosocial health during the diagnosis, disease, treatment, isolation and recovery phases. Norway is a low endemic country of tuberculosis. Most patients are immigrants, and some of them have recently arrived in the country. Patients undergoing treatment for drug-resistant tuberculosis endure prolonged and demanding treatment that could affect their psychosocial health. METHODS: This qualitative study conducted 16 in-depth interviews with individuals aged 18 years and above who were diagnosed with drug-resistant tuberculosis. All participants completed the treatment between 2008 and 2020. Fourteen participants were immigrants, and eight of them had resided in Norway for less than four years before diagnosis. Data analysis followed the six-phase reflexive thematic analysis framework, focusing on identifying patterns in participants' experiences, thoughts, expectations and attitudes. RESULTS: The narratives of the participants highlighted the complexities of navigating the diagnosis of drug-resistant tuberculosis, treatment, side effects and life after treatment. Immigrants encountered additional challenges, including language barriers and adapting to new social environments. All participants reported experiencing physical health issues that additionally affected their mental health and social activity. Several participants had a delayed or prolonged diagnosis that complicated their disease trajectory. Participants with suspected or confirmed contagious pulmonary tuberculosis underwent hospital isolation for periods ranging from weeks to six months. The participants reported mental health issues, social isolation and stigma, however few were offered follow-up by a psychologist. Many participants had persistent problems at the time of the interviews. Three main themes emerged from the analysis: Delayed and prolonged diagnosis; Psychosocial impact of isolation during treatment; The life after tuberculosis. CONCLUSION: This study highlights the enduring impact of drug-resistant tuberculosis on patients and the significance of timely diagnosis, psychosocial support and post-treatment follow-up. The participants universally faced serious implications of the disease, including stigma and isolation. Participants who experienced delayed diagnosis, reflected on missed early intervention opportunities. We recommend further research in low endemic countries to evaluate the international and local recommendations on psychosocial support.
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Investigación Cualitativa , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Noruega/epidemiología , Masculino , Femenino , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/psicología , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Adulto , Persona de Mediana Edad , Emigrantes e Inmigrantes/psicología , Emigrantes e Inmigrantes/estadística & datos numéricos , Adulto Joven , Entrevistas como Asunto , Antituberculosos/uso terapéuticoRESUMEN
Clofazimine is an antimycobacterial, anti-inflammatory agent used in the management of leprosy and multidrug-resistant (MDR) tuberculosis. It has high oral bioavailability and poor solubility because of which prolonged administration of the drug results in its accumulation as intracellular biocrystals in tissue macrophages. We describe the case of a female patient in her early 30s who was on therapy for MDR tuberculosis. She presented with streaky haemoptysis of 6 months. Radiographic examination showed no abnormality in pulmonary vasculature and parenchyma. Bronchoscopy showed diffuse red-coloured flecks in tracheal and bronchial mucosa. The retrieved bronchoalveolar lavage (BAL) fluid was reddish-purple in colour. Microscopic examination of BAL fluid showed reddish clofazimine crystal deposition in alveolar macrophages. Serum and BAL clofazimine levels were performed using high performance liquid chromatography which confirmed high drug levels. She developed reddish discolouration of the skin during therapy due to clofazimine deposition. A diagnosis of pulmonary clofazimine crystal deposition syndrome causing pseudohaemoptysis was established.
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Clofazimina , Hemoptisis , Clofazimina/uso terapéutico , Humanos , Femenino , Hemoptisis/etiología , Hemoptisis/diagnóstico , Adulto , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/complicaciones , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Síndrome , Líquido del Lavado Bronquioalveolar/citología , Diagnóstico DiferencialRESUMEN
INTRODUCTION: Early diagnosis of tuberculosis (TB) and universal access to drug-susceptibility testing (DST) are critical elements of the WHO End TB Strategy. Current rapid tests (e.g., Xpert® MTB/RIF and Ultra-assays) can detect rifampicin resistance-conferring mutations, but cannot detect resistance to Isoniazid and second-line anti-TB agents. Although Line Probe Assay is capable of detecting resistance to second-line anti-TB agents, it requires sophisticated laboratory infrastructure and advanced skills which are often not readily available in settings replete with TB. A rapid test capable of detecting Isoniazid and second-line anti-TB drug resistance is highly needed. METHODS: We conducted a diagnostic accuracy study to evaluate a new automated Xpert MTB/XDR 10-colour assay for rapid detection of Isoniazid and second-line drugs, including ethionamide, fluoroquinolones, and injectable drugs (Amikacin, Kanamycin, and Capreomycin). Positive Xpert MTB/RIF respiratory specimens were prospectively collected through routine diagnosis and surveillance of drug resistance at the Central TB Reference Laboratory in Tanzania. Specimens were tested by both Xpert XDR assay and LPA against culture-based phenotypic DST as the reference standard. FINDINGS: We analysed specimens from 151 TB patients with a mean age (SD) of 36.2 (12.7) years. The majority (n = 109, 72.2%) were males. The sensitivity for Xpert MTB/XDR was 93.5% (95% CI, 87.4-96.7); for Isoniazid, 96.6 (95% CI, 92.1-98.6); for Fluoroquinolone, 98.7% (95% Cl 94.8-99.7); for Amikacin, 96.6%; and (95% CI 92.1-98.6) for Ethionamide. Ethionamide had the lowest specificity of 50% and the highest was 100% for Fluoroquinolone. The diagnostic performance was generally comparable to that of LPA with slight variations between the two assays. The non-determinate rate (i.e., invalid M. tuberculosis complex detection) of Xpert MTB/XDR was 2·96%. CONCLUSION: The Xpert MTB/XDR demonstrated high sensitivity and specificity for detecting resistance to Isoniazid, Fluoroquinolones, and injectable agents. This assay can be used in clinical settings to facilitate rapid diagnosis of mono-isoniazid and extensively drug-resistant TB.
Asunto(s)
Antituberculosos , Isoniazida , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis , Sensibilidad y Especificidad , Humanos , Tanzanía , Isoniazida/farmacología , Antituberculosos/farmacología , Adulto , Femenino , Masculino , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Persona de Mediana Edad , Pruebas de Sensibilidad Microbiana/métodos , Adulto Joven , Adolescente , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Estudios Prospectivos , Anciano , Técnicas de Diagnóstico Molecular/métodosRESUMEN
Drug-resistant tuberculosis (TB) poses a significant public health concern in South Africa due to its complexity in diagnosis, treatment, and management. This study assessed the diagnostic performance of the Xpert MTB/XDR test for detecting drug resistance in patients with TB by using archived sputum sediments. This study analyzed 322 samples collected from patients diagnosed with TB between 2016 and 2019 across South Africa, previously characterized by phenotypic and genotypic methods. The Xpert MTB/XDR test was evaluated for its ability to detect resistance to isoniazid (INH), ethionamide (ETH), fluoroquinolones (FLQ), and second-line injectable drugs (SLIDs) compared with phenotypic drug susceptibility testing (pDST) and whole-genome sequencing (WGS). Culture, Xpert MTB/RIF Ultra, and Xpert MTB/RIF (G4) tests were performed to determine sensitivity and agreement with this test for TB detection. The sensitivities using a composite reference standard, pDST, and sequencing were >90% for INH, FLQ, amikacin (AMK), kanamycin (KAN), and capreomycin (CAP) resistance, meeting the WHO target product profile criteria for this class. A lower sensitivity of 65.9% (95% CI: 57.1-73.6) for ETH resistance was observed. The Xpert MTB/XDR showed a sensitivity of 98.3% (95% CI: 96.1-99.3) and specificity of 100% (95% CI: 86.7-100) compared with culture, a positive percent agreement (PPA) of 98.8% (95% CI: 93.7-99.8) and negative percent agreement (NPA) of 100.0% (95% CI: 78.5-100.0) compared with G4, and a PPA of 99.5% (95% CI: 97.3-99.9) and NPA of 100.0% (95% CI: 78.5-100.0) compared with Xpert MTB/RIF Ultra for detecting Mycobacterium tuberculosis. The test offers a promising solution for the rapid detection of drug-resistant TB and could significantly enhance control efforts in this setting.
Asunto(s)
Antituberculosos , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis , Sensibilidad y Especificidad , Humanos , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Sudáfrica , Antituberculosos/farmacología , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Extensivamente Resistente a Drogas/diagnóstico , Tuberculosis Extensivamente Resistente a Drogas/microbiología , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Esputo/microbiología , Secuenciación Completa del Genoma , Técnicas de Diagnóstico Molecular/métodos , Farmacorresistencia Bacteriana MúltipleRESUMEN
Despite available global efforts and funding, Tuberculosis (TB) continues to affect a considerable number of patients worldwide. Policy makers and stakeholders set clear goals to reduce TB incidence and mortality, but the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) complicate the reach of these goals. Drug-resistance TB needs to be diagnosed rapidly and accurately to effectively treat patients, prevent the transmission of MDR-TB, minimise mortality, reduce treatment costs and avoid unnecessary hospitalisations. In this narrative review, we provide a comprehensive overview of laboratory methods for detecting drug resistance in MTB, focusing on phenotypic, molecular and other drug susceptibility testing (DST) techniques. We found a large variety of methods used, with the BACTEC MGIT 960 being the most common phenotypic DST and the Xpert MTB/RIF being the most common molecular DST. We emphasise the importance of integrating phenotypic and molecular DST to address issues like resistance to new drugs, heteroresistance, mixed infections and low-level resistance mutations. Notably, most of the analysed studies adhered to the outdated definition of XDR-TB and did not consider the pre-XDR definition, thus posing challenges in aligning diagnostic methods with the current landscape of TB resistance.
Asunto(s)
Antituberculosos , Tuberculosis Extensivamente Resistente a Drogas , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis , Fenotipo , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Antituberculosos/uso terapéutico , Antituberculosos/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Pruebas de Sensibilidad Microbiana/métodos , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Extensivamente Resistente a Drogas/diagnóstico , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Tuberculosis Extensivamente Resistente a Drogas/microbiología , Farmacorresistencia Bacteriana Múltiple/genética , Técnicas de Diagnóstico Molecular/métodos , Valor Predictivo de las PruebasRESUMEN
Tuberculosis (TB) is the world's deadliest infectious disease, with over 1.5 million deaths and 10 million new cases reported anually. The causative organism Mycobacterium tuberculosis (Mtb) can take nearly 40 d to culture, a required step to determine the pathogen's antibiotic susceptibility. Both rapid identification and rapid antibiotic susceptibility testing of Mtb are essential for effective patient treatment and combating antimicrobial resistance. Here, we demonstrate a rapid, culture-free, and antibiotic incubation-free drug susceptibility test for TB using Raman spectroscopy and machine learning. We collect few-to-single-cell Raman spectra from over 25,000 cells of the Mtb complex strain Bacillus Calmette-Guérin (BCG) resistant to one of the four mainstay anti-TB drugs, isoniazid, rifampicin, moxifloxacin, and amikacin, as well as a pan-susceptible wildtype strain. By training a neural network on this data, we classify the antibiotic resistance profile of each strain, both on dried samples and on patient sputum samples. On dried samples, we achieve >98% resistant versus susceptible classification accuracy across all five BCG strains. In patient sputum samples, we achieve ~79% average classification accuracy. We develop a feature recognition algorithm in order to verify that our machine learning model is using biologically relevant spectral features to assess the resistance profiles of our mycobacterial strains. Finally, we demonstrate how this approach can be deployed in resource-limited settings by developing a low-cost, portable Raman microscope that costs <$5,000. We show how this instrument and our machine learning model enable combined microscopy and spectroscopy for accurate few-to-single-cell drug susceptibility testing of BCG.
Asunto(s)
Antituberculosos , Aprendizaje Automático , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis , Espectrometría Raman , Espectrometría Raman/métodos , Mycobacterium tuberculosis/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana/métodos , Antituberculosos/farmacología , Farmacorresistencia Bacteriana , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis/tratamiento farmacológico , Tuberculosis/microbiología , Isoniazida/farmacologíaRESUMEN
Importance: Rifampin-resistant tuberculosis treatment regimens require electrocardiographic (ECG) monitoring due to the use of multiple QTc-prolonging agents. Formal 12-lead ECG devices represent a significant burden in resource-constrained clinics worldwide and a potential barrier to treatment scale-up in some settings. Objective: To evaluate the diagnostic accuracy of a handheld 6-lead ECG device within resource-constrained clinics. Design, Setting, and Participants: This diagnostic study was performed within a multicenter, pragmatic (broad eligibility criteria with no exclusions for randomized participants), phase 3 rifampin-resistant tuberculosis treatment trial (BEAT Tuberculosis [Building Evidence for Advancing New Treatment for Tuberculosis]) in South Africa. A total of 192 consecutive trial participants were assessed, and 191 were recruited for this substudy between January 21, 2021, and March 27, 2023. A low proportion (3 of 432 [0.7%]) of all screened trial participants were excluded due to a QTc interval greater than 450 milliseconds. Triplicate reference standard 12-lead ECG results were human calibrated with readers blinded to 6-lead ECG results. Main Outcomes and Measures: Diagnostic accuracy, repeatability, and feasibility of a 6-lead ECG device. Results: A total of 191 participants (median age, 36 years [IQR, 28-45 years]; 81 female participants [42.4%]; 91 participants [47.6%] living with HIV) with a median of 4 clinic visits (IQR, 3-4 visits) contributed 2070 and 2015 12-lead and 6-lead ECG assessments, respectively. Across 170 participants attending 489 total clinic visits where valid triplicate QTc measurements were available for both devices, the mean 12-lead QTc measurement was 418 milliseconds (range, 321-519 milliseconds), and the mean 6-lead QTc measurement was 422 milliseconds (range, 288-574 milliseconds; proportion of variation explained, R2 = 0.4; P < .001). At a QTc interval threshold of 500 milliseconds, the 6-lead ECG device had a negative predictive value of 99.8% (95% CI, 98.8%-99.9%) and a positive predictive value of 16.7% (95% CI, 0.4%-64.1%). The normal expected range of within-individual variability of the 6-lead ECG device was high (±50.2 milliseconds [coefficient of variation, 6.0%]) relative to the 12-lead ECG device (±22.0 milliseconds [coefficient of variation, 2.7%]). The mean (SD) increase in the 12-lead QTc measurement during treatment was 10.1 (25.8) milliseconds, with 0.8% of clinic visits (4 of 489) having a QTc interval of 500 milliseconds or more. Conclusions and Relevance: This study suggests that simplified, handheld 6-lead ECG devices are effective triage tests that could reduce the need to perform 12-lead ECG monitoring in resource-constrained settings.
Asunto(s)
Electrocardiografía , Humanos , Femenino , Masculino , Adulto , Electrocardiografía/instrumentación , Electrocardiografía/métodos , Sudáfrica , Persona de Mediana Edad , Síndrome de QT Prolongado/diagnóstico , Reproducibilidad de los Resultados , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Configuración de Recursos LimitadosRESUMEN
This study evaluated the performance of cobas MTB and cobas MTB-RIF/INH for the diagnosis of tuberculosis and detection of rifampicin (RIF) and isoniazid (INH) resistance. Adults presenting with pulmonary tuberculosis symptoms were recruited in South Africa, Moldova, and India. Performance of cobas MTB was assessed against culture, whereas cobas MTB-RIF/INH was assessed using phenotypic drug susceptibility testing and whole-genome sequencing as composite reference standards. Xpert MTB/RIF (Xpert) or Xpert MTB/RIF Ultra (Ultra) was used as a comparator. The overall sensitivity and specificity of cobas MTB were 95% (95% CI, 93%-96%) and 96% (95% CI, 95%-97%). Among smear-negatives, the sensitivity of cobas MTB was 75% (95% CI, 66%-83%). Among participants tested with both cobas MTB and Xpert, sensitivity was 96% (95% CI, 94%-97%) for cobas MTB and 95% (95% CI, 93%-97%) for Xpert. Among participants tested with both cobas MTB and Ultra, sensitivity was 88% (95% CI, 81%-92%) for cobas MTB and 89% (95% CI, 83%-93%) for Ultra. Sensitivity and specificity of cobas MTB-RIF/INH for RIF and INH detection were 90% (95% CI, 84%-94%) and 100% (95% CI, 99%-100%), and 89% (95% CI, 84%-93%) and 99.5% (95% CI, 98%-100%), respectively. The cobas MTB and cobas MTB-RIF/INH assays exhibited high performance in a diverse population and present a suitable option for molecular detection of tuberculosis and RIF and INH resistance.