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BACKGROUND: Chronic pulmonary aspergillosis (CPA) is known to complicate patients with post-tubercular lung disease. However, some evidence suggests that CPA might co-exist in patients with newly-diagnosed pulmonary tuberculosis (P.TB) at diagnosis and also develop during therapy. The objective of this study was to confirm the presence of CPA in newly diagnosed P.TB at baseline and at the end-of-TB-therapy. MATERIALS AND METHODS: This prospective longitudinal study included newly diagnosed P.TB patients, followed up at third month and end-of-TB-therapy with symptom assessment, anti-Aspergillus IgG antibody and imaging of chest for diagnosing CPA. RESULTS: We recruited 255 patients at baseline out of which 158 (62%) completed their follow-up. Anti-Aspergillus IgG was positive in 11.1% at baseline and 27.8% at end-of-TB-therapy. Overall, proven CPA was diagnosed in 7% at baseline and 14.5% at the end-of-TB-therapy. Around 6% patients had evidence of aspergilloma in CT chest at the end-of-TB-therapy. CONCLUSIONS: CPA can be present in newly diagnosed P.TB patients at diagnosis and also develop during anti-tubercular treatment. Patients with persistent symptoms or developing new symptoms during treatment for P.TB should be evaluated for CPA. Whether patients with concomitant P.TB and CPA, while receiving antitubercular therapy, need additional antifungal therapy, needs to be evaluated in future studies.
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Aspergilose Pulmonar , Tuberculose Pulmonar , Humanos , Masculino , Feminino , Aspergilose Pulmonar/epidemiologia , Aspergilose Pulmonar/tratamento farmacológico , Aspergilose Pulmonar/complicações , Aspergilose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/diagnóstico , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto , Estudos Longitudinais , Incidência , Idoso , Anticorpos Antifúngicos/sangue , Doença Crônica , Seguimentos , Imunoglobulina G/sangue , Antituberculosos/uso terapêutico , Aspergillus/isolamento & purificação , Aspergillus/imunologia , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVE: Female genital tuberculosis (FGTB) is an important type of extrapulmonary tuberculosis (TB) associated with morbidity especially infertility in developing countries. Laparoscopy may be difficult and hazardous in FGTB. The aim of the study was to observe the difficulties and complications of laparoscopy in FGTB cases. MATERIALS AND METHODS: It was a prospective study over 12 years' period on 412 cases of diagnostic laparoscopy performed on FGTB cases with infertility. All patients underwent history taking and clinical examination and endometrial sampling for acid-fast bacilli (AFB) microscopy, culture, polymerase chain reaction (PCR), gene Xpert (last 212 cases) and histopathological evidence of epithelioid granuloma. Another 412 cases of diagnostic laparoscopy in the absence of FGTB performed during same time were taken as controls from the pool of non-TB cases. Various difficulties and complications were noted in both groups and statistical analysis was done. RESULTS: Mean age, parity, body mass index and duration of infertility were 26.8 versus 25.4 years, 0.32 versus 0.28, 23.15 versus 25.28 Kg/m 2 and 4.15 versus 5.12 years, respectively. Primary and secondary infertility was seen in 78.6% and 20.38% of cases in the study group and 74.75% and 25.24% in the control group, respectively. Endometrial biopsy showed AFB microscopy in 5.3%, culture in 6.3%, epithelioid granuloma in 15.77% and on peritoneal biopsy granuloma in 6.55%, positive PCR in 368 (89.32%) and positive gene Xpert in 38 out of 212 (17.92%, out of last 212 cases). Definite findings of FGTB were seen in 171 (41.50%) cases. Probable findings of FGTB were seen in 241 (58.49%) cases. Various complications were difficulty in the creation of pneumoperitoneum or insertion of trocar and cannula in 16.74% and 13.10% of cases as compared to 1.94% and 1.69% in the control group. Excessive bleeding was seen in 5.09% versus 0.97% cases, respectively. Various injuries observed were bowel injury in 1.69% versus 0.24% cases (small bowel in 1.21% vs. 0.24%, large bowel in 0.48% vs. 0.1%), while bladder injury was seen in 0.97% versus 0.24% cases, subacute intestinal obstruction was seen in 5.8% versus 0.72% cases respectively while flare up of TB was seen in 5.09% versus 0% in cases and controls, respectively. Wound infection was seen in 8.48% versus 1.25% cases, respectively. INTERPRETATION AND CONCLUSION: FGTB is associated with increased complications and difficulties as compared to laparoscopy in other cases.
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BACKGROUND: To evaluate the effect of metformin on the plasma levels of rifampicin, isoniazid, and pyrazinamide in patients with drug-sensitive pulmonary tuberculosis being treated with first-line antituberculosis treatment (ATT) and to assess the influence of gene polymorphisms on the metabolic pathway of metformin and plasma levels of antitubercular drugs. METHODS: Nondiabetic adults aged 18-60 years with pulmonary tuberculosis were randomized to either the standard ATT (ATT group) or ATT plus metformin (METRIF group) groups in a phase IIB clinical trial. An intensive pharmacokinetic study with blood collection at 0 hour (predosing), followed by 1, 2, 4, 6, 8, and 12 hours after dosing was conducted during the first month of treatment in a subset of 60 study participants after a minimum of 14 doses. Plasma concentrations of rifampicin, isoniazid, pyrazinamide, and metformin were measured by high-performance liquid chromatography using validated methods, and pharmacokinetic parameters and OCT1 and MATE1 gene polymorphisms were compared between the groups. RESULTS: Significant increases in the clearance of rifampicin, isoniazid, and pyrazinamide were observed in patients in the METRIF group (n = 29) compared with those in the ATT group (n = 31). The AA genotypes of the single-nucleotide polymorphism of rs2289669 (MATE1) in the METRIF group showed a significantly decreased area under the concentration-time curve to the last observation point and increased clearance of rifampicin. CONCLUSIONS: Metformin altered rifampicin and isoniazid plasma concentrations in patients receiving antituberculosis treatment for pulmonary tuberculosis with little effect on sputum conversion at the end of treatment. Studies with larger sample sizes are needed to understand host drug-drug interactions.
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Background & objectives: Female genital tuberculosis (FGTB) is an important variety of extrapulmonary TB causing significant morbidity, especially infertility, in developing countries like India. The aim of this study was to evaluate the laparoscopic findings of the FGTB. Methods: This was a cross-sectional study on 374 cases of diagnostic laparoscopy performed on FGTB cases with infertility. All patients underwent history taking and clinical examination and endometrial sampling/biopsy for acid-fast bacilli, microscopy, culture, PCR, GeneXpert (only last 167 cases) and histopathological evidence of epithelioid granuloma. Diagnostic laparoscopy was performed in all the cases to evaluate the findings of FGTB. Results: Mean age, parity, body mass index and duration of infertility were 27.5 yr, 0.29, 22.6 kg/m2 and 3.78 years, respectively. Primary infertility was found in 81 per cent and secondary infertility in 18.18 per cent of cases. Endometrial biopsy was positive for AFB microscopy in 4.8 per cent, culture in 6.4 per cent and epithelioid granuloma in 15.5 per cent. Positive peritoneal biopsy granuloma was seen in 5.88 per cent, PCR in 314 (83.95%) and GeneXpert in 31 (18.56%, out of last 167 cases) cases. Definite findings of FGTB were seen in 164 (43.86%) cases with beaded tubes (12.29%), tubercles (32.88%) and caseous nodules (14.96%). Probable findings of FGTB were seen in 210 (56.14%) cases with pelvic adhesions (23.52%), perihepatic adhesions (47.86%), shaggy areas (11.7%), pelvic adhesions (11.71%), encysted ascites (10.42%) and frozen pelvis in 3.7 per cent of cases. Interpretation & conclusions: The finding of this study suggests that laparoscopy is a useful modality to diagnose FGTB with a higher pickup rate of cases. Hence it should be included as a part of composite reference standard.
Assuntos
Infertilidade Feminina , Laparoscopia , Tuberculose dos Genitais Femininos , Gravidez , Humanos , Feminino , Tuberculose dos Genitais Femininos/complicações , Tuberculose dos Genitais Femininos/diagnóstico , Tuberculose dos Genitais Femininos/patologia , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/epidemiologia , Estudos Transversais , Laparoscopia/efeitos adversos , GranulomaRESUMO
Extra-pulmonary tuberculosis (EPTB) continues to be difficult to diagnose. Novel biomarkers in biological specimens offer promise. Detection of Mycobacterium tuberculosis (Mtb) DNA in urine could prove useful in diagnosis of EPTB, possibly due to disseminated disease or micro-abscesses reported in kidneys. The current study was designed to detect Mtb DNA in stored urine samples from patients with EPTB. Diagnosis of EPTB was reached using Microbiological Reference Standards (MRS) on samples from the disease site using WHO Recommended Diagnostics (WRD), [smear microscopy, liquid culture (MGIT-960)] and GX (molecular WRD, mWRD) and Comprehensive reference standards [CRS, clinical presentation, microbiological reference standards, radiology, histopathology]. GX-Ultra was performed on urine samples stored in -80oC deep freezer, retrospectively. Of 70 patients, 51 (72.9%) were classified as confirmed TB, 11 (15.7%) unconfirmed TB, and 8 (11.4%) unlikely TB. GX-Ultra in urine samples demonstrated sensitivity of 52.9% and specificity of 57.9% against MRS, and higher sensitivity of 56.5% and specificity of 100% against CRS. The sensitivity and specificity of GX-Ultra in urine was 53.6% and 75% for pus sample subset and 52.2% and 53.3% for fluid sample subset. Urine being non-invasive and easy to collect, detection of Mtb DNA using mWRD in urine samples is promising for diagnosis of EPTB.
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Tuberculose Extrapulmonar , Humanos , Estudos Retrospectivos , Rim , Microscopia , DNARESUMO
BACKGROUND: Metformin, by reducing intracellular Mycobacterium tuberculosis growth, can be considered an adjunctive therapy to anti-tuberculosis treatment (ATT). We determined whether metformin with standard ATT reduces time to sputum culture conversion and tissue inflammation in adults with pulmonary tuberculosis (PTB). METHODS: In a randomized, 8-week, clinical trial, newly diagnosed, culture-positive PTB patients were randomized to standard ATT (HREZ = control arm) or standard ATT plus daily 1000 mg metformin (MET-HREZ = Metformin with Rifampicin [METRIF] arm) for 8 weeks during 2018-2020 at 5 sites in India. The primary end point was time to sputum culture conversion by liquid culture during 8 weeks of ATT. Plasma inflammatory markers were estimated in a subset. A Cox proportional hazard model was used to estimate time and predictors of culture conversion. RESULTS: Of the 322 patients randomized, 239 (74%) were male, and 212 (66%) had bilateral disease on chest radiograph with 54 (18%) showing cavitation. The median time to sputum culture conversion by liquid culture was 42 days in the METRIF arm and 41 days in the control arm (hazard ratio, 0.8; 95% confidence interval [CI], .624-1.019). After 8 weeks of ATT, cavitary lesions on X-ray (7, 5.3% vs 18, 12.9%; relative risk, 0.42; 95% CI, .18-.96; Pâ =â .041) and inflammatory markers were significantly lower in the METRIF arm. Higher body mass index and lower sputum smear grading were associated with faster sputum culture conversion. CONCLUSIONS: The addition of metformin to standard ATT did not hasten sputum culture conversion but diminished excess inflammation, thus reducing lung tissue damage as seen by faster clearance on X-ray and reduced inflammatory markers. CLINICAL TRIALS REGISTRATION: Clinical Trial Registry of India (CTRI/2018/01/011176).
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Metformina , Mycobacterium tuberculosis , Tuberculose Pulmonar , Adulto , Antituberculosos/uso terapêutico , Feminino , Humanos , Inflamação/complicações , Masculino , Metformina/uso terapêutico , Escarro/microbiologia , Tuberculose Pulmonar/diagnósticoRESUMO
In the absence of a sensitive and specific diagnostic modality capable of detecting all forms of tuberculosis (TB), proteomics may identify specific Mycobacterium tuberculosis (M.tb) proteins in urine, with a potential as biomarkers. To identify candidate biomarkers for TB, proteome profile of urine from pulmonary TB patients was compared with non-disease controls (NDC) and disease controls (DC, Streptococcus pneumonia infected patients) using a combination of two-dimensional difference gel electrophoresis (2D-DIGE) and liquid chromatography tandem mass spectrometry (LCMS/MS). Eleven differentially expressed host proteins and Eighteen high abundant M.tb proteins were identified. Protein-protein interactome (PPI) and functional enrichment analyses like Gene Ontologies, Reactome pathway etc. demonstrated that the human proteins mainly belong to extracellular space and show physiological pathways for immune response and hematological disorders. Whereas, M.tb proteins belong to the cell periphery, plasma membrane and cell wall, and demonstrated catalytic, nucleotide binding and ATPase activities along with other functional processes. The study findings provide valuable inputs about the biomarkers of TB and shed light on the probable disease consequences as an outcome of the bacterial pathogenicity.
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Mycobacterium tuberculosis , Tuberculose Pulmonar , Tuberculose , Biomarcadores/metabolismo , Humanos , Mycobacterium tuberculosis/metabolismo , Proteômica/métodos , Espectrometria de Massas em Tandem/métodos , Tuberculose/microbiologia , Tuberculose Pulmonar/diagnóstico , Eletroforese em Gel Diferencial BidimensionalRESUMO
Emerging evidence shows co-infection with atypical bacteria in coronavirus disease 2019 (COVID-19) patients. Respiratory illness caused by atypical bacteria such as Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila may show overlapping manifestations and imaging features with COVID-19 causing clinical and laboratory diagnostic issues. We conducted a prospective study to identify co-infections with SARS-CoV-2 and atypical bacteria in an Indian tertiary hospital. From June 2020 to January 2021, a total of 194 patients with laboratory-confirmed COVID-19 were also tested for atypical bacterial pathogens. For diagnosing M. pneumoniae, a real-time polymerase chain reaction (PCR) assay and serology (IgM ELISA) were performed. C. pneumoniae diagnosis was made based on IgM serology. L. pneumophila diagnosis was based on PCR or urinary antigen testing. Clinical and epidemiological features of SARS-CoV-2 and atypical bacteria-positive and -negative patient groups were compared. Of the 194 patients admitted with COVID-19, 17 (8.8%) were also diagnosed with M. pneumoniae (n = 10) or C. pneumoniae infection (n = 7). Confusion, headache, and bilateral infiltrate were found more frequently in the SARS CoV-2 and atypical bacteria co-infection group. Patients in the M. pneumoniae or C. pneumoniae co-infection group were more likely to develop ARDS, required ventilatory support, had a longer hospital length of stay, and higher fatality rate compared to patients with only SARS-CoV-2. Our report highlights co-infection with bacteria causing atypical pneumonia should be considered in patients with SARS-CoV-2 depending on the clinical context. Timely identification of co-existing pathogens can provide pathogen-targeted treatment and prevent fatal outcomes of patients infected with SARS-CoV-2 during the current pandemic.
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Formas Bacterianas Atípicas/isolamento & purificação , COVID-19/patologia , Infecções por Chlamydophila/epidemiologia , Coinfecção/epidemiologia , Doença dos Legionários/epidemiologia , Pneumonia por Mycoplasma/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Chlamydophila pneumoniae/isolamento & purificação , Feminino , Humanos , Índia , Legionella pneumophila/isolamento & purificação , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Mycoplasma pneumoniae/isolamento & purificação , Estudos Prospectivos , SARS-CoV-2 , Índice de Gravidade de Doença , Adulto JovemRESUMO
Emerging reports of SARS-CoV-2 breakthrough infections entail methodical genomic surveillance for determining the efficacy of vaccines. This study elaborates genomic analysis of isolates from breakthrough infections following vaccination with AZD1222/Covishield and BBV152/Covaxin. Variants of concern B.1.617.2 and B.1.1.7 responsible for cases surge in April-May 2021 in Delhi, were the predominant lineages among breakthrough infections.
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COVID-19/virologia , SARS-CoV-2/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , ChAdOx1 nCoV-19/administração & dosagem , Feminino , Genoma Viral/genética , Genômica , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Filogenia , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , Vacinação , Vacinas de Produtos Inativados/administração & dosagem , Adulto JovemRESUMO
BACKGROUND & OBJECTIVES: There is a need for an affordable, easy, high-sensitivity test usable at the peripheral health facility for diagnosis of drug-resistant (DR) tuberculosis (TB) to interrupt disease transmission. Nucleic acid amplification tests (NAATs) for early detection of DR-TB are ideal to bring testing near to the patient. TruenatTM MTB (Mycobacterium tuberculosis) and TruenatTM MTB-RIF (rifampicin) is an indigenous chip-based real-time polymerase chain reaction (PCR) based test for detection of multidrug-resistant (MDR) TB. The test involves extraction of DNA using automated, battery operated Trueprep instrument and real-time PCR performed on the Truelab analyzer. We report here multicentric validation of Truenat MTB-RIF for detection of DR-TB in suspected DR-TB patients. METHODS: Consecutive patients aged 18-65 yr, with symptoms suggestive of TB and with a history of previous treatment, reporting to the National TB Elimination Programme (NTEP) clinics under four national institutes, namely AIIMS (All India Institute of Medical Sciences, New Delhi), NITRD (National Institute of Tuberculosis and Respiratory Diseases, New Delhi), NIRT (National Institute for Research in Tuberculosis, Chennai) and ICMR-National JALMA Institute for Leprosy and other Mycobacterial Diseases, Agra, were included in the study. Two sputum samples (one spot and one morning) were collected from each patient, after obtaining informed written consent. The samples were subjected to smear, GeneXpert and MGIT 960 culture (and drug susceptibility testing to RIF) (surrogate for MDR-TB) to serve as reference tests. The samples were coded to ensure blinding and subjected to Truenat MTB-RIF. Truenat MTB-RIF Version 1.5 was used for testing 1084 samples for RIF resistance, while Version 2.0 was used to test another 1201 samples. RESULTS: Truenat MTB-RIF Version 1.5 in comparison with comprehensive laboratory reference standards yielded sensitivity and specificity of 76.2 and 94.7 per cent, respectively for the detection of RIF resistance in 1084 samples, collected across four sites. Based on the analysis of discordant samples, Version 2.0 of Truenat was developed by the manufacturer and this was further tested on additional 1201 samples, yielding a sensitivity of 87.5 per cent and specificity of 99.5 per cent. INTERPRETATION & CONCLUSIONS: Multicentric trial of TruenatTM MTB-RIF demonstrated a great potential of this point of care NAAT for detection of MDR-TB. The test would be useful in limited resource settings and inaccessible areas without need for any additional infrastructure.
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Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose Pulmonar , Adolescente , Adulto , Idoso , Humanos , Índia , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Rifampina/farmacologia , Rifampina/uso terapêutico , Sensibilidade e Especificidade , Escarro , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/genética , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico , Adulto JovemRESUMO
BACKGROUND & OBJECTIVES: : Early case detection is essential to interrupt transmission and to prevent further spread of tuberculosis (TB) in high endemic settings. Nucleic acid amplification tests (NAATs) with visual read-outs are ideal as point-of-care tests. Truenat™ MTB is an indigenous chip-based NAAT for detection of Mycobacterium tuberculosis, which involves extraction of DNA and real-time polymerase chain reaction (PCR) using portable, automated, battery-operated instruments. The current multicentric study was aimed to evaluate Truenat for detection of MTB in sputum samples obtained from patients with presumptive pulmonary TB with reference to culture as gold standard and Xpert as a comparator. METHODS: : The study was conducted at four sites, namely ICMR-National Institute for Research in Tuberculosis, Chennai; All India Institute of Medical Sciences, New Delhi; ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Agra; and National Institute of TB and Respiratory Diseases, New Delhi. Patients suspected to have TB were screened for eligibility. Two sputum samples were collected from each patient. Tests included smear, Xpert and Truenat directly from the sputum sample and culture by Lowenstein-Jensen (L-J) medium and MGIT960 from decontaminated pellets. Sample used for Truenat assay was coded. Resolution of Truenat false positives was done using an in-house PCR with TRC4 primers. RESULTS: : The study enrolled 2419 presumptive TB patients after screening 2465 patients, and 3541 sputum samples were collected from the enrolled patients. Results of 2623 samples were available for analysis. Truenat showed a positivity rate of 48.5 per cent as compared to 37.0 per cent by Xpert. The sensitivities of Truenat and Xpert were was 88.3 and 79.7 per cent, respectively in comparison with culture. INTERPRETATION & CONCLUSIONS: : Truenat MTB identified more positives among culture-confirmed samples than Xpert and had higher sensitivity. In addition, other advantageous operational features of Truenat MTB were identified which would be useful in field settings.
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Mycobacterium tuberculosis , Tuberculose Pulmonar , Humanos , Índia , Mycobacterium tuberculosis/genética , Padrões de Referência , Sensibilidade e Especificidade , Escarro , Tuberculose Pulmonar/diagnósticoRESUMO
STUDY OBJECTIVE: To assess diagnostic value of polymerase chain reaction (PCR) in endometrial aspirates (EAs) in comparison with conventional tests for diagnosis of female genital tuberculosis (TB) and to find agreement between EA PCR done for endometrial TB and laparoscopic findings of pelvic TB in women with unexplained infertility. DESIGN: Prospective observational cohort study. SETTING: Tertiary care hospital. PATIENTS: A total of 732 infertile females screened and 385 enrolled to undergo procedure to obtain EAs. INTERVENTIONS: EAs were tested by conventional tests (histopathology, acid-fast bacilli, Lowenstein-Jensen staining, liquid culture) and PCR for Mycobacterium tuberculosis. Patients with positive conventional tests were started on antitubercular treatment (ATT). Patients with negative conventional tests underwent laparohysteroscopy irrespective of PCR results to assess changes of tubercular infection in the pelvis. Peritoneal washings were also sent for liquid culture and PCR for TB, and suspicious lesions were biopsied at laparohysteroscopy. Findings at laparoscopy upgraded the diagnosis in these women. EAPCR results were analyzed to find agreement with the findings at laparoscopy. MEASUREMENTS AND MAIN RESULTS: Conventional tests were positive in 8 of 385 (2%) patients. PCR was positive in 58.1% (nâ¯=â¯224) of endometrial samples, with sensitivity of 62.5% (95% confidence interval [CI], 24.49-91.48), specificity of 41.91% (95% CI, 36.88-47.07), positive predictive value of 2.23% (95% CI, 1.31-3.78), negative predictive value of 98.14% (95% CI, 95.53-99.24), and a diagnostic accuracy of 42.34% (95% CI, 37.35-47.45) with conventional tests. A total of 265 patients underwent laparoscopy, of whom 165 were PCR positive and 100 were PCR negative. Laparoscopic findings suggestive of TB were found in 39.3% of patients who were PCR positive and 9% of patients who were PCR negative. Kappa agreement was 0.25, suggesting fair agreement between PCR and laparoscopy. CONCLUSION: PCR as a stand-alone diagnostic test for endometrial TB is not justified to confirm diagnosis and initiate ATT. The addition of laparohysteroscopy improves diagnostic yield for genital TB. Referring patients with a suspicion of female genital TB to tertiary care for 1-time laparoscopy is better than initiating ATT solely on the basis of PCR results.
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Infertilidade Feminina/diagnóstico , Laparoscopia , Técnicas de Diagnóstico Molecular/métodos , Mycobacterium tuberculosis/genética , Tuberculose dos Genitais Femininos/diagnóstico , Adulto , Biópsia por Agulha , Estudos de Coortes , Testes Diagnósticos de Rotina , Endométrio/microbiologia , Endométrio/patologia , Endométrio/cirurgia , Feminino , Humanos , Infertilidade Feminina/etiologia , Infertilidade Feminina/microbiologia , Infertilidade Feminina/patologia , Laparoscopia/métodos , Masculino , Técnicas de Diagnóstico Molecular/tendências , Mycobacterium tuberculosis/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Tuberculose dos Genitais Femininos/complicações , Tuberculose dos Genitais Femininos/microbiologia , Tuberculose dos Genitais Femininos/patologia , Adulto JovemRESUMO
STUDY OBJECTIVE: To study the effect of antitubercular treatment (ATT) on the laparoscopic abdominopelvic and fallopian tube findings in female genital tuberculosis (FGBT). DESIGN: Prospective cohort (Canadian Task Force classification II2). SETTING: Tertiary referral center in northern India. PATIENTS: Fifty women with infertility and diagnosed with FGTB on laparoscopy, histopathology findings, or endometrial sampling (acid-fast bacilli culture, granuloma on histopathology, positive polymerase chain reaction). INTERVENTIONS: Diagnostic laparoscopy in all women diagnosed with FGTB before and after a 6-month course of ATT (2 months of rifampicin, isoniazid, pyrazinamide, and ethambutol, followed by 4 months of rifampicin and isoniazid). All procedures were performed by the same surgeon between June 2012 and May 2014. MEASUREMENTS AND MAIN RESULTS: The mean patient age was 28.7 years, mean parity was 0.9, and mean body mass index was 23.6 kg/m(2). Infertility was seen in all 50 women (66% primary infertility, 34% secondary infertility), with a mean duration of 6.06 years. Abnormal laparoscopic findings of FGTB included tubercles in the pelvic peritoneum, fallopian tube, and ovary in 27 women (54%) before ATT and in only 1 (2.04%) woman after ATT (p < .001). Caseous nodules and encysted ascites were seen in 4 women (8%) before ATT, and in no women after ATT (p < .001); however, there was no change from before ATT to after ATT in the rate of pelvic adhesions (42% vs 42.5%) and perihepatic adhesions (56% vs 58%). Laparoscopic findings in fallopian tubes included hydrosalpinx (32%), pyosalpinx (4%), beaded tubes (12%), nonvisualization of tube (20%), and tubal blockage on the right side (56%), left side (50%), and both sides (38%) before ATT. Hydrosalpinx, beaded tubes, and nonvisualized tube were seen in 33.4%, 4.1%, and 20.8% cases, respectively, after ATT; however, free spill increased to 52% on the right side and 50% on left side after ATT. CONCLUSION: ATT improves laparoscopic findings in FGTB with infertility. However, advanced fibrotic lesions (eg, pelvic and perihepatic adhesions, bilateral blocked tubes) do not improve with ATT.
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Antituberculosos/uso terapêutico , Doenças das Tubas Uterinas/patologia , Tubas Uterinas/patologia , Infertilidade Feminina/patologia , Laparoscopia , Aderências Teciduais/patologia , Tuberculose dos Genitais Femininos/patologia , Adulto , Animais , Doenças das Tubas Uterinas/complicações , Doenças das Tubas Uterinas/tratamento farmacológico , Tubas Uterinas/virologia , Feminino , Humanos , Índia , Infertilidade Feminina/tratamento farmacológico , Infertilidade Feminina/etiologia , Gravidez , Estudos Prospectivos , Aderências Teciduais/complicações , Aderências Teciduais/tratamento farmacológico , Resultado do Tratamento , Tuberculose dos Genitais Femininos/complicações , Tuberculose dos Genitais Femininos/tratamento farmacológicoRESUMO
BACKGROUND & OBJECTIVES: Tuberculosis (TB) is a common infection in patients on haemodialysis. There is a definite role of treatment of latent TB (LTB) in these patients. However, diagnosis of LTB in these patients by tuberculin skin test (TST) is unreliable. There is suggestion that interferon gamma release assay (IGRA) will be more reliable test for diagnosis of LTB in this setting. Thus, we evaluated value of IGRA and TST for the diagnosis of LTB in patients on dialysis in an Indian setting. METHODS: Patients with end stage kidney disease on dialysis were included. Patients with active TB were excluded. Each patient was subjected to TST (induration of ≥10 mm was taken as positive) and QuantiFERON TB Gold In-Tube test (QFT-GIT) for diagnosis of LTB. RESULTS: A total of 185 patients were included; 129 (69.7%) were males and mean age was 36.7 ± 12.3 yr. Past history of TB was present in 18 (9.7%) patients. One hundred and thirty four (72.4%) patients had scar of BCG vaccination. QFT-GIT test was positive in 66 (36%), TST in 32 (17%) and both in 13 (7%) patients. Of the 66 patients positive with QFT-GIT, only 13 (19.6%) were positive for TST. Of the 32 patients positive with TST, only 13 (40.6%) were positive with QFT-GIT; 100 (54%) patients were negative for both the tests. Overall, 85 (45.9%) patients were positive for either of the two tests. Poor agreement was shown between the two methods. On logistic regression analysis, odds of QFT-GIT to be positive in patients with BCG vaccination was 1.23 and with history of TB 0.99, both being insignificant. odds of tuberculin skin test to be positive in patients with BCG vaccination was 1.04 and with history of TB 0.99, both again being insignificant. INTERPRETATION & CONCLUSIONS: Our findings showed that more number of patients (36%) on haemodialysis were positive for QuantiFERON Gold In-Tube test as compared to TST (17%). There was poor agreement between the two tests. No significant effect of BCG vaccination and history of TB in past was observed on both tests.
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Testes de Liberação de Interferon-gama , Interferon gama/metabolismo , Tuberculose Latente/diagnóstico , Diálise Renal/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Vacina BCG , Feminino , Humanos , Índia , Falência Renal Crônica/patologia , Tuberculose Latente/patologia , Masculino , Pessoa de Meia-Idade , Teste TuberculínicoRESUMO
The burden of tuberculosis (TB) is disproportionate in tropical and subtropical regions, where parasitic coinfections are common. Given the significant geographical overlap between TB and intestinal parasitic infections, it is important to consider the implications of intestinal parasitic infections for the TB pandemic. Intestinal parasitic infections have been theorized to increase vulnerability to TB by altering the inflammatory milieu, inducing undernutrition that blunts the immune response, and affecting drug pharmacokinetics. In this perspective piece, we provide a background of the epidemiological and immunological evidence that links parasitic infections to increased risk of TB progression and worse treatment outcomes. We also identify gaps in our knowledge and call for increased research on TB-parasitic coinfections to ensure action on a potentially widespread TB comorbidity.
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Extra-pulmonary TB (EPTB) is difficult to diagnose due to paucibacillary nature of disease. Current study evaluated accuracy of Truenat MTB and MTB-Rif Dx (TN), for detection of Mycobacterium tuberculosis and resistance to rifampicin. Samples were collected from 2103 treatment naive adults with presumptive EPTB, and tested by smear microscopy, liquid culture (LC) (MGIT-960) and GeneXpert MTB/RIF (GX) (Microbiological Reference Standards, MRS). TN results were compared to MRS and Composite Reference Standards (CRS, Microbiology, histopathology, radiology, clinical features prompting decision to treat, response to treatment). CRS grouped patients into 551 confirmed, 1096 unconfirmed, and 409 as unlikely TB. TN sensitivity and specificity was 73.7% and 90.4% against GX. Against LC, Overall sensitivity of GX was 67.6%, while that of TN was 62.3%. Highest sensitivity by TN was observed in pus samples (89%) and highest specificity (92%) in CSF samples, similar to GX. TN sensitivity was better in fluid and biopsy samples and slightly inferior for lymph node aspirates compared to GX. TN sensitivity for RIF resistance detection was slightly superior to GX. TN and GX results were further compared to Clinical Reference Standards. TN detected 170 TB patients initiated on treatment missed by GX, while GX detected 113 such patients missed by TN. Of 124 samples with RIF resistance discordance between GX and TN, GX reported 103/124 as sensitive, 3/124 as indeterminate and 18 as resistant (13/18 samples had low/very low DNA load) while TN reported RIF resistance indeterminate in 103/111 low/very low DNA load samples. Due to paucibacillary nature of EPTB samples, culture yield was poor and phenotypic drug susceptibility testing failed to resolve the discordance. The study establishes TN at par with GX and can be utilized for quick and accurate diagnosis of EPTB.
Assuntos
Rifampina , Sensibilidade e Especificidade , Tuberculose Extrapulmonar , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Farmacorresistência Bacteriana/genética , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/isolamento & purificação , Rifampina/uso terapêutico , Tuberculose Extrapulmonar/diagnóstico , Tuberculose Extrapulmonar/tratamento farmacológicoRESUMO
BACKGROUND: Female genital tuberculosis (FGTB) is a common cause of infertility in developing countries. Its diagnosis is difficult due to its paucibacillary nature, with no single test having high sensitivity and specificity. This study is to share the experience of using Composite Reference Standard (CRS) for the diagnosis of FGTB. METHODS: This is a prospective study conducted between September 2017 to June 2019, over 100 infertile females found to have FGTB on composite reference standard which consisted of acid-fast bacilli on microscopy or culture, histopathological evidence of epithelioid granuloma, positive gene Xpert on endometrial sample or definite or probable finding of FGTB on laparoscopy. RESULTS: A total of 100 infertile women (78% primary, 22% secondary) found to have FGTB on CRS were enrolled in this study. Mean age, body mass index, parity and duration of infertility were 28.2 years, 23.17 kg/m2, 0.24 ± 0.12 and 2.41 years respectively. Various symptoms were scanty menses (16%), irregular cycle (7%), dysmenorrhea (11%), pelvic pain (11%). Various signs were vaginal discharge (65%), adnexal mass (6%), tubo-ovarian mass on ultrasound (15%), abnormal hysterosalpingography findings (57.14%), positive polymerase chain reaction test (65%) and abnormal hysteroscopy (82.2%). The positive findings on CRS were positive AFB on microscopy or culture (3%), positive gene Xpert (28%) (done in some cases), epithelioid granuloma on histopathology (13%), definite findings on laparoscopy like tubercles, caseous nodules and beaded tubes in (57.19%) patients while probable findings of FGTB like straw colored fluid in POD, extensive dense pelvic, peri-tubal, peri-ovarian adhesions; hydrosalpinx; tubo-ovarian mass; thick fibrosed tubes; mid tubal block; peri hepatic adhesions (Fitz Hugh Curtis Syndrome); hyperemia of tubes/blue uterus on chromotubation were seen in (48.8%) patients. All patients found to be positive on CRS were given 6 months of anti-tubercular therapy. CONCLUSION: This study demonstrates the high reliability of use of composite reference standard for diagnosis of FGTB.
Assuntos
Infertilidade Feminina , Neoplasias Ovarianas , Tuberculose dos Genitais Femininos , Gravidez , Humanos , Feminino , Adulto , Tuberculose dos Genitais Femininos/complicações , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/etiologia , Estudos Prospectivos , Reprodutibilidade dos Testes , Granuloma/complicações , Neoplasias Ovarianas/complicaçõesRESUMO
Context: The COVID-19 vaccination drive globally was supposedly a game-changing event. However, the emerging variants of the virus and waning immunity over time posed new challenges for breakthrough infections. Standing at the frontline of defense against COVID-19, healthcare personnel (HCP) were vulnerable to such infections. Aims: This study estimates i) the vaccine breakthrough infections (VBI) among HCP following exposure to COVID-19 cases, and ii) the mean interval between the second dose of vaccine and laboratory-confirmed SARS-CoV-2 infection. Materials and Methods: A cross-sectional study was conducted including 385 HCP with a history of exposure to COVID-19 cases during January and February 2022. Demographic details and clinical and vaccination history were collected from the test forms and the Web-based hospital management system. Laboratory testing of COVID-19 was carried out by real-time RT-PCR test. Results: The majority of the HCP were males (262; 68.05%) and nurses (180; 46.75%) by occupation. Two doses of vaccines were received by 278 (87.7%) HCP. VBI was confirmed in 185 (66.55%) HCP. No significant difference in VBI between the COVAXIN and COVISHIELD recipients (P = 0.69) was observed. The interval between the second dose and confirmed SARS-CoV-2 infection was significantly higher (P < 0.00001) in COVAXIN recipients (median 228 days) than in COVISHIELD recipients (median 95 days). Conclusions: The incidence of VBI was very high among the HCP, but not statistically different among the COVAXIN and COVISHIELD-recipients. Waning immunity over time suggests boosting immunity with a third dose because of emerging variants.
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There is an unmet need for tools that permit diagnosis of Tuberculosis (TB) that are affordable, low-tech, and can differentiate Mycobacterium tuberculosis (M.tb) from non-tuberculous mycobacteria (NTM). In this study, we have developed a strip-based assay to detect the activity of a unique Carbapenem Resistance Factor A (CrfA) enzyme present only in M.tb. The strip comprises of PVDF (Polyvinylidene fluoride) membrane that has an immobilized anti-CrfA antibody to capture the CrfA enzyme from M.tb lysate. Lysate of mycobacteria is applied to the strip, washed, and incubated in the presence of chromogenic reporter dye which is a substrate for CrfA. A change in the color of the dye that is readily visible to the naked eye is the readout. We evaluated lysates from M.tb and various NTMs namely, M. abscessus, M. chelonae, M. avium, M. obuense, M. paraintracellulare, M. kansasi, including the patient-derived sputum samples. The strip assay selectively identified only those samples containing M.tb. Based on this evidence, this new assay enables the identification and differentiation of M.tb from NTMs in patient sputum samples. As this tool can be simple to use, therefore has the potential to serve the unmet need for diagnosis of TB and NTM infections in resource-limited settings.
Assuntos
Infecções por Mycobacterium não Tuberculosas , Mycobacterium tuberculosis , Tuberculose , Humanos , Micobactérias não Tuberculosas , Tuberculose/diagnóstico , Tuberculose/microbiologia , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Escarro/microbiologiaRESUMO
Rapid, cost-effective, and sensitive diagnostic assays are essential for global tuberculosis (TB) control, especially in high TB burden, resource-limited settings. The current study was designed to evaluate diagnostic accuracy of Truenat MTB-Rif Dx (MolBio) in children less than 18 years of age, with symptoms suggestive of TB. Gastric aspirate, induced sputum, and broncho-alveolar lavage samples were subjected simultaneously to AFB-smear, GeneXpert MTB/RIF, liquid culture (MGIT-960) and Truenat MTB-Rif Dx. The index-test results were evaluated against microbiological reference standards (MRS). Truenat MTB-Rif Dx had a sensitivity of 57.1%, specificity of 92% against MRS. The sensitivity and specificity of the Truenat MTB-RIF Dx compared with liquid culture was 58.7% and 87.5% while GeneXpert MTB/RIF was 56% and 91.4%. The performance of both GeneXpert MTB/RIF and Truenat MTB-Rif Dx are comparable. Result of our study demonstrates that Truenat MTB-Rif can aid in early and efficient diagnosis of TB in children.