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A prospective study of the prevalence of tuberculosis and bacteraemia in Bangladeshi children with severe malnutrition and pneumonia including an evaluation of Xpert MTB/RIF assay.

ABSTRACT: Severe malnutrition is a risk factor for pneumonia due to a wide range of pathogens but aetiological data are limited and the role of Mycobacterium tuberculosis is uncertain.We prospectively investigated severely malnourished young children (<5 years) with radiological pneumonia admitted over a 15-month period. Investigations included blood culture, sputa for microscopy and mycobacterial culture. Xpert MTB/RIF assay was introduced during the study. Study children were followed for 12 weeks following their discharge from the hospital.405 eligible children were enrolled, with a median age of 10 months. Bacterial pathogens were isolated from blood culture in 18 (4.4%) children, of which 72% were Gram negatives. Tuberculosis was confirmed microbiologically in 7% (27/396) of children that provided sputum - 10 by culture, 21 by Xpert MTB/RIF assay, and 4 by both tests. The diagnostic yield from induced sputum was 6% compared to 3.5% from gastric aspirate. Sixty (16%) additional children had tuberculosis diagnosed clinically that was not microbiologically confirmed. Most confirmed tuberculosis cases did not have a positive contact history or positive tuberculin test. The sensitivity and specificity of Xpert MTB/RIF assay compared to culture was 67% (95% CI: 24-94) and 92% (95% CI: 87-95) respectively. Overall case-fatality rate was 17% and half of the deaths occurred in home following discharge from the hospital.TB was common in severely malnourished Bangladeshi children with pneumonia. X-pert MTB/RIF assay provided higher case detection rate compared to sputum microscopy and culture. The high mortality among the study children underscores the need for further research aimed at improved case detection and management for better outcomes.

SUBMITTER: Chisti MJ

PROVIDER: S-EPMC3973596 | biostudies-other | 2014

REPOSITORIES: biostudies-other

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A prospective study of the prevalence of tuberculosis and bacteraemia in Bangladeshi children with severe malnutrition and pneumonia including an evaluation of Xpert MTB/RIF assay.

Chisti Mohammod Jobayer MJ Graham Stephen M SM Duke Trevor T Ahmed Tahmeed T Ashraf Hasan H Faruque Abu Syed Golam AS La Vincente Sophie S Banu Sayera S Raqib Rubhana R Salam Mohammed Abdus MA

PloS one 20140402 4

<h4>Background</h4>Severe malnutrition is a risk factor for pneumonia due to a wide range of pathogens but aetiological data are limited and the role of Mycobacterium tuberculosis is uncertain.<h4>Methods</h4>We prospectively investigated severely malnourished young children (<5 years) with radiological pneumonia admitted over a 15-month period. Investigations included blood culture, sputa for microscopy and mycobacterial culture. Xpert MTB/RIF assay was introduced during the study. Study childr ...[more]

PMID: 24695758

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Project description:BackgroundXpert MTB/RIF Ultra (Xpert Ultra) might have higher sensitivity than its predecessor, Xpert MTB/RIF (Xpert), but its role in tuberculous meningitis diagnosis is uncertain. We aimed to compare Xpert Ultra with Xpert for the diagnosis of tuberculous meningitis in HIV-uninfected and HIV-infected adults.MethodsIn this prospective, randomised, diagnostic accuracy study, adults (≥16 years) with suspected tuberculous meningitis from a single centre in Vietnam were randomly assigned to cerebrospinal fluid testing by either Xpert Ultra or Xpert at baseline and, if treated for tuberculous meningitis, after 3-4 weeks of treatment. Test performance (sensitivity, specificity, and positive and negative predictive values) was calculated for Xpert Ultra and Xpert and compared against clinical and mycobacterial culture reference standards. Analyses were done for all patients and by HIV status.FindingsBetween Oct 16, 2017, and Feb 10, 2019, 205 patients were randomly assigned to Xpert Ultra (n=103) or Xpert (n=102). The sensitivities of Xpert Ultra and Xpert for tuberculous meningitis diagnosis against a reference standard of definite, probable, and possible tuberculous meningitis were 47·2% (95% CI 34·4-60·3; 25 of 53 patients) for Xpert Ultra and 39·6% (27·6-53·1; 21 of 53) for Xpert (p=0·56); specificities were 100·0% (95% CI 92·0-100·0; 44 of 44) and 100·0% (92·6-100·0; 48 of 48), respectively. In HIV-negative patients, the sensitivity of Xpert Ultra was 38·9% (24·8-55·1; 14 of 36) versus 22·9% (12·1-39·0; eight of 35) by Xpert (p=0·23). In HIV co-infected patients, the sensitivities were 64·3% (38·8-83·7; nine of 14) for Xpert Ultra and 76·9% (49·7-91·8; ten of 13) for Xpert (p=0·77). Negative predictive values were 61·1% (49·6-71·5) for Xpert Ultra and 60·0% (49·0-70·0) for Xpert. Against a reference standard of mycobacterial culture, sensitivities were 90·9% (72·2-97·5; 20 of 22 patients) for Xpert Ultra and 81·8% (61·5-92·7; 18 of 22) for Xpert (p=0·66); specificities were 93·9% (85·4-97·6; 62 of 66) and 96·9% (89·5-91·2; 63 of 65), respectively. Six (22%) of 27 patients had a positive test by Xpert Ultra after 4 weeks of treatment versus two (9%) of 22 patients by Xpert.InterpretationXpert Ultra was not statistically superior to Xpert for the diagnosis of tuberculous meningitis in HIV-uninfected and HIV-infected adults. A negative Xpert Ultra or Xpert test does not rule out tuberculous meningitis. New diagnostic strategies are urgently required.FundingWellcome Trust and the Foundation for Innovative New Diagnostics.

Project description:BackgroundThe aim of this study was to evaluate the role of Xpert MTB/RIF assay in the detection of Mycobacterium tuberculosis for differentiating tuberculosis intrathoracic lymphadenopathy from sarcoidosis intrathoracic lymphadenopathy.MethodsThe patients who were suspected to having sarcoidosis or tuberculosis intrathoracic lymphadenopathy at the Shanghai Pulmonary Hospital between October 1, 2020 and June 30, 2021 were retrospectively evaluated in this study. All patients underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and Xpert analysis. Differences in clinical and radiological features were recorded. The diagnostic performances of EBUS-TBNA Xpert, acid-fast bacilli, culture, and peripheral blood QuantiFERON-TB Gold (QFT) for differentiating sarcoidosis from tuberculosis intrathoracic lymphadenopathy were analyzed.ResultsA total of 119 patients were included in this analysis. Of those, 83 patients were finally diagnosed with sarcoidosis (N = 50) and tuberculosis (N = 33) intrathoracic lymphadenopathy. Young individuals were more likely to have tuberculosis versus sarcoidosis intrathoracic lymphadenopathy (P = 0.006). Markers of inflammation, including fever, leukocytes, and serum ferritin levels, were significantly higher in tuberculosis versus sarcoidosis intrathoracic lymphadenopathy (P < 0.01). Bilateral lung involvement and symmetry intrathoracic lymphadenopathy were more common in sarcoidosis intrathoracic lymphadenopathy (P < 0.01). In addition, the longest diameter of intrathoracic lymphadenopathy (in cm) was significantly larger in sarcoidosis intrathoracic lymphadenopathy (P = 0.001). However, the largest diameter of lung lesions was significantly shorter (P = 0.005). The sensitivity and specificity values of Xpert and QFT for differentiating these two diseases were 69.70% and 100%, and 96.43% and 91.84%, respectively.ConclusionXpert MTB/RIF is recommended for the diagnosis of tuberculosis intrathoracic lymphadenopathy using EBUS-TBNA samples. A negative QFT suggests the exclusion of the diagnosis of tuberculosis intrathoracic lymphadenopathy.

Project description:The detection and management of Mycobacterium tuberculosis complex (MTBC) infection, the causative agent of tuberculosis (TB), in macaques, including cynomolgus macaques (Macaca fascicularis), are of significant concern in research and regions where macaques coexist with humans or other animals. This study explored the utility of the Xpert MTB/RIF Ultra assay, a widely adopted molecular diagnostic tool to diagnose tuberculosis (TB) in humans, to detect DNA from the Mycobacterium tuberculosis complex in clinical samples obtained from cynomolgus macaques. This investigation involved a comprehensive comparative analysis, integrating established conventional diagnostic methodologies, assessing oropharyngeal-tracheal wash (PW) and buccal swab (BS) specimen types, and follow-up assessments at 3-month, 6-month, and 12-month intervals. Our results demonstrated that the Xpert MTB/RIF Ultra assay was able to detect MTBC in 12 of 316 clinical samples obtained from cynomolgus macaques, presenting a potential advantage over bacterial culture and chest radiographs. The Xpert MTB/RIF Ultra assay exhibited exceptional sensitivity (100%) at the animal level, successfully detecting all macaques positive for M. tuberculosis as confirmed by traditional culture methods. The use of PW samples revealed that 5 positive samples from 99 (5.1%) were recommended for testing, compared to 0 samples from 99 buccal swab (BS) samples (0.0%). In particular, the definitive diagnosis of TB was confirmed in three deceased macaques by MTB culture, which detected the presence of the bacterium in tissue autopsy. Our findings demonstrate that the implementation of the Xpert MTB/RIF Ultra assay, along with prompt isolation measures, effectively reduced active TB cases among cynomolgus macaques over a 12-month period. These findings highlight the advance of the Xpert MTB/RIF Ultra assay in TB diagnosis and its crucial role in preventing potential outbreaks in cynomolgus macaques. With its rapidity, high sensitivity, and specificity, the Xpert MTB/RIF Ultra assay can be highly suitable for use in reference laboratories to confirm TB disease and effectively interrupt TB transmission.

Project description:The aim of this study was to evaluate the performance of Xpert MTB/RIF Ultra (Ultra) compared with its predecessor, Xpert MTB/RIF (Xpert), in the diagnosis of tuberculosis (TB) in a low TB incidence country. Retrospective analysis was performed on 689 clinical samples received between 2015 and 2018, on which Xpert was performed, and on 715 samples, received between 2018 and 2020, on which Ultra was performed. Samples were pulmonary (n = 830) and extrapulmonary (n = 574) in nature, and a total of 264 were culture positive for Mycobacterium tuberculosis complex (MTBC). The diagnostic performance of both assays was analyzed using culture as the reference standard. The sensitivity of Ultra for culture positive (smear positive and smear negative) MTBC samples, was 93.2% (110/118) compared with 82.2% (120/146) for Xpert (P = 0.0078). In smear negative-culture positive samples, Ultra had a sensitivity of 74.2% (23/31) versus 36.11% (13/36) for Xpert (P = 0.0018). Specificity of both assays was comparable at 94.8% (566/597) for Ultra and 95.8% (520/543) for Xpert (P = 0.4475). The sensitivity of Ultra and Xpert assays among exclusively pulmonary samples was 95.3% (82/86) and 90.3% (84/93), respectively (P = 0.1955), and 87.5% (28/32) and 67.9% (36/53), respectively, among extrapulmonary samples (P = 0.0426). Ultra showed improved performance compared with Xpert in a low TB incidence setting, particularly in smear negative and extrapulmonary MTBC disease. The specificity of Ultra was lower than Xpert, however, this was not statistically significant. IMPORTANCE The study demonstrates the improved sensitivity of the Ultra compared with the Xpert, particularly in smear negative TB disease, for both pulmonary and extrapulmonary samples in a low TB incidence setting. Cycle threshold (Ct) value for both assays was found to positively correlate with time to TB culture positivity, suggesting that Ct and semiquantitative results could be used as indicators of sample MTBC bacillary burden, and thus, perhaps, of transmission potential. This may have implications for the designation of patient isolation precautions.

Project description:BackgroundTuberculosis (TB) is a major public health problem in low and middle-income countries. Early detection and enrolment of TB cases is a challenge for National TB Programs.ObjectiveTo understand the performance and feasibility for scale-up of Xpert MTB/RIF assay for the TB diagnosis in Nepal.DesignImplementation research employed mixed-method sequential explanatory design. The results of Xpert MTB/RIF assay were analysed in 26 TB diagnostic centres where Xpert machines had been installed before 2015. In-depth interviews and focus group discussions were conducted with stakeholders, purposively selected to represent experiences in centres that were functioning well, poorly or not functioning.ResultsDuring a one-year period in 2015/16, 23,075 Xpert MTB/RIF assays were performed in 21 diagnostic centres with 22,288 people also tested by sputum microscopy. Among these, 77% had concordant (positive or negative) results, demonstrating fair agreement (Kappa score, 0.3) between test results. Test failure and positivity rates in diagnostic centres ranged from 2.6% to 13.4% and 6.5% to 49%, respectively. The number of cartridges per positive result varied from 2.3 to 10.2. Xpert assay was positive in 3314 (15% of all cases) sputum smear microscopy negative cases. Of 4280 bacteriologically confirmed cases by Xpert assay, 355 (8%) were rifampicin resistant. Xpert machines were no longer functioning regularly throughout the year in 5 diagnostic centres. The main barriers for effective implementation of Xpert in Nepal were the lack of: timely supply of cartridges; replacement of damaged modules; maintenance of Xpert machines; and stock verification for timely procurement of cartridges. Inadequate laboratory infrastructure for maintaining functional Xpert equipment further challenges implementation and scale-up.ConclusionThe implementation of Xpert MTB/RIF assay has increased case-finding of TB and MDR-TB in Nepal. However, there is a need to improve laboratory performance and strengthen laboratory infrastructure for optimal utilisation and scale-up of Xpert.

Dataset Information

A prospective study of the prevalence of tuberculosis and bacteraemia in Bangladeshi children with severe malnutrition and pneumonia including an evaluation of Xpert MTB/RIF assay.

Publications

A prospective study of the prevalence of tuberculosis and bacteraemia in Bangladeshi children with severe malnutrition and pneumonia including an evaluation of Xpert MTB/RIF assay.

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