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Diagnosis of paediatric tuberculosis using sputum induction in Botswana: programme description and findings.

ABSTRACT: SETTING:Four public hospitals in Botswana, a high tuberculosis (TB) burden setting. OBJECTIVES:To assess the feasibility and utility of sputum induction in the diagnosis of paediatric TB. DESIGN:From 2008 to 2010, children aged ?18 years referred for suspected pulmonary TB underwent sputum induction. Confirmed TB was defined as the presence of at least one of the signs and symptoms suggestive of TB and positive Mycobacterium tuberculosis culture. Information on TB-associated symptoms (cough, fatigue, night sweats, low appetite, chest pain, weight loss, haemoptysis and contact with a TB case) was collected for three risk groups: human immunodeficiency virus (HIV) positive children, HIV-negative children aged <3 years and HIV-negative children aged ?3 years. RESULTS:The median age of the 1394 subjects who underwent sputum induction was 3.8 years (IQR 1.3-8.4); 373 (27%) were HIV-positive, 419 (30%) were HIV-negative and 602 (43%) had unknown HIV status. TB was confirmed in 84 (6.0%); cases were more likely to have weight loss, chest pain or TB household contacts. There were no serious complications attributable to sputum induction during and after the procedure; only 0.8% (9/1174) of patients reported minor complications. CONCLUSIONS:In Botswana, paediatric sputum induction was feasible, safe and assisted bacteriological confirmation in a subgroup of children treated for TB.

SUBMITTER: Joel DR

PROVIDER: S-EPMC6223014 | biostudies-other | 2014 Mar

REPOSITORIES: biostudies-other

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Diagnosis of paediatric tuberculosis using sputum induction in Botswana: programme description and findings.

Joel D R DR Steenhoff A P AP Mullan P C PC Phelps B R BR Tolle M A MA Ho-Foster A A Mabikwa V V Kgathi B G BG Ncube R R Anabwani G M GM

The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease 20140301 3

<h4>Setting</h4>Four public hospitals in Botswana, a high tuberculosis (TB) burden setting.<h4>Objectives</h4>To assess the feasibility and utility of sputum induction in the diagnosis of paediatric TB.<h4>Design</h4>From 2008 to 2010, children aged ≤18 years referred for suspected pulmonary TB underwent sputum induction. Confirmed TB was defined as the presence of at least one of the signs and symptoms suggestive of TB and positive Mycobacterium tuberculosis culture. Information on TB-associate ...[more]

PMID: 24670571

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Project description:BackgroundTuberculosis (TB) diagnosis in children is a major challenge with up to 94% of children with TB treated empirically in TB high-burden countries. Paediatric tuberculosis (PTB) remains a major cause of morbidity and mortality globally, particularly in developing countries. Most deaths/morbidity from TB in paediatrics could be prevented with early diagnosis and appropriate treatment. The main objective of this systematic review is to examine the evidence whether real-time polymerase chain reaction assay could be the most accurate clinical laboratory diagnostic methodology for the Mycobacterium tuberculosis (MTB) detection in paediatrics.MethodsWe will search MEDLINE/PubMed, EMBASE, BIOSIS, LILACS, Cochrane Infectious Diseases Group Specialised Register (CIDG SR), Global Health, and CINAHL for published studies that recruited children less than 16 years of age being investigated for Mycobacterium tuberculosis (MTB) infection using real-time polymerase chain reaction assay accompanied by mycobacteriological culture investigation as the reference standard. There will be no restriction regarding the language, date of publication, and publication status. We will include randomised controlled trials and observational studies (cohort, cross-sectional) in the review. Selection of studies, data extraction and management, assessment of risk of bias, and quality of evidence will be performed by two independent reviewers (EB and BC). A third researcher will be consulted in case of discrepancies. Depending on the availability and quality of the data, a meta-analysis will be performed. Otherwise, findings will be qualitatively reported.DiscussionTo our knowledge, this is the first systematic review and meta-analysis assessing the detection of MTB from all clinical sample types using real-time polymerase chain reaction assay in paediatric population. This review will make available evidence on the accuracy, approach, and interpretation of results of this assay in the context of MTB diagnosis which will meet an urgent need, considering the challenges of MTB diagnosis in paediatrics.Systematic review registrationPROSPERO CRD42018104052.

Project description:BACKGROUND:Xpert® MTB/RIF (Xpert) has high sensitivity for diagnosing tuberculosis (TB) compared to sputum-smear microscopy (smear) and can reduce time-to-diagnosis, time-to-treatment and potentially unfavorable patient-level treatment outcome. METHODS:People living with HIV (PLHIV) initiating antiretroviral therapy at 22 HIV clinics were enrolled and underwent systematic screening for TB (August 2012-November 2014). GeneXpert instruments were deployed following a stepped-wedge design at 13 centers from October 2012-June 2013. Treatment outcomes classified as an unfavorable outcome (died, treatment failure or loss-to-follow-up) or favorable outcome (cured and treatment completed). To determine outcome, smear was performed at month 5 or 6. Empiric treatment was defined as initiating treatment without/before receiving TB-positive results. Adjusting for intra-facility correlation, we compared patient-level treatment outcomes between patients screened using smear (smear arm)- and Xpert-based algorithms (Xpert arm). RESULTS:Among 6041 patients enrolled (smear arm, 1816; Xpert arm, 4225), 256 (199 per 2985 and 57 per 1582 person-years of follow-up in Xpert and smear arms, respectively; adjusted incidence rate ratio, 9.07; 95% confidence interval [CI]: 4.70-17.48; p?<?0.001) received TB diagnosis and were treated. TB treatment outcomes were available for 203 patients (79.3%; Xpert, 157; smear, 46). Unfavorable outcomes were reported for 21.7% (10/46) in the smear and 13.4% (21/157) in Xpert arm (adjusted hazard ratio, 1.40; 95% CI: 0.75-2.26; p?=?0.268). Compared to smear, in Xpert arm median days from sputum collection to TB treatment was 6?days (interquartile range [IQR] 2-17 versus 22?days [IQR] 3-51), p?=?0.005; patients with available sputum test result had microbiologically confirmed TB in 59.0% (102/173) versus 41.9% (18/43), adjusted Odds Ratio [aOR], 2.00, 95% CI: 1.01-3.96, p?=?0.048). In smear arm empiric treatment was 68.4% (39/57) versus 48.7% (97/199), aOR, 2.28, 95% CI: 1.24-4.20, p?=?0.011), compared to Xpert arm. CONCLUSIONS:TB treatment outcomes were similar between the smear and Xpert arms. However, compared to the smear arm, more patients in the Xpert arm received a TB diagnosis, had a microbiologically confirmed TB, and had a shorter time-to-treatment, and had a lower empiric treatment. Further research is recommended to identify potential gaps in the Botswana health system and similar settings. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT02538952. Retrospectively registered on 2 September 2015.

Project description:INTRODUCTION:There is lack of information on the proportion of new smear-positive pulmonary tuberculosis (PTB) patients treated with a 6-month thrice-weekly regimen under Revised National Tuberculosis Control Programme (RNTCP) who develop recurrent TB after successful treatment outcome. OBJECTIVE:To estimate TB recurrence among newly diagnosed PTB patients who have successfully completed treatment and to document endogenous reactivation or re-infection. Risk factors for unfavourable outcomes to treatment and TB recurrence were determined. METHODOLOGY:Adult (aged ? 18 yrs) new smear positive PTB patients initiated on treatment under RNTCP were enrolled from sites in Tamil Nadu, Karnataka, Delhi, Maharashtra, Madhya Pradesh and Kerala. Those declared "treatment success" at the end of treatment were followed up with 2 sputum examinations each at 3, 6 and 12 months after treatment completion. MIRU-VNTR genotyping was done to identify endogenous re-activation or exogenous re-infection at TB recurrence. TB recurrence was expressed as rate per 100 person-years (with 95% confidence interval [95%CI]). Regression models were used to identify the risk factors for unfavourable response to treatment and TB recurrence. RESULTS:Of the1577 new smear positive PTB patients enrolled, 1565 were analysed. The overall cure rate was 77% (1207/1565) and treatment success was 77% (1210 /1565). The cure rate varied from 65% to 86%. There were 158 of 1210 patients who had TB recurrence after treatment success. The pooled TB recurrence estimate was 10.9% [95%CI: 0.2-21.6] and TB recurrence rate per 100 person-years was 12.7 [95% CI: 0.4-25]. TB recurrence per 100 person-years varied from 5.4 to 30.5. Endogenous reactivation was observed in 56 (93%) of 60 patients for whom genotyping was done. Male gender was associated with TB recurrence. CONCLUSION:A substantial proportion of new smear positive PTB patients successfully treated with 6 -month thrice-weekly regimen have TB recurrence under program settings.

Project description:Suboptimal diagnostics for pulmonary tuberculosis (PTB) drives use of 'trial-of-antibiotics (non-tuberculosis)' in an attempt to distinguish PTB patients from those with bacterial lower respiratory tract infection (LRTI). The underlying assumption-that patients with LRTI will report 'response' to broad-spectrum antibiotics, while those with PTB will not-has minimal evidence base for such a widely used intervention. Numerous potential causes of misclassification include bacterial super-infection of active PTB, placebo effect, and antimicrobial resistance (AMR). The main aim of this systematic review is to collate available evidence on the performance of trial-of-antibiotics as a diagnostic test and to explore the timing, interpretation, and decision-making process.We will search MEDLINE, Embase, and Global Health using the Ovid platform for published studies that recruited adults being investigated for PTB, performed trial-of-antibiotics accompanied by mycobacteriological investigations, and reported both diagnostic test outcomes at the individual level. Following article selection, two authors will independently review titles and abstracts against eligibility criteria then perform full-text screening and extraction into a spreadsheet. We will conduct a risk of bias assessment at the level of the study using QUADAS-2 (University of Bristol) tool that assesses diagnostic evaluation work in four domains: (1) patient selection, (2) the index test, (3) the reference standard, and (4) patient flow and timing of tests. We will perform a narrative synthesis and, where possible, meta-analyses addressing our primary outcome. Our protocol adheres to the standards recommended by the PRISMA-P.Pooling all available evidence on the accuracy, approach, and interpretation of results of trial-of-antibiotics in the context of PTB diagnosis will meet an urgent need, considering the widespread utilisation and potential for antimicrobial resistance. We therefore believe that our findings will have impact on policy and that they will inform the design of future detailed investigations into this important diagnostic approach.PROSPERO CRD42017083915.

Dataset Information

Diagnosis of paediatric tuberculosis using sputum induction in Botswana: programme description and findings.

Publications

Diagnosis of paediatric tuberculosis using sputum induction in Botswana: programme description and findings.

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