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Scientific Reports Jan 2021In Sub-Saharan Africa, African giant pouched rats (Cricetomys gambianus) are trained to identify TB patients by smelling sputum. We conducted a systematic review and... (Meta-Analysis)
Meta-Analysis
In Sub-Saharan Africa, African giant pouched rats (Cricetomys gambianus) are trained to identify TB patients by smelling sputum. We conducted a systematic review and meta-analysis of the data to see if this novel method is comparable to traditional laboratory screening and detection methods like Ziehl-Neelsen stain-based assays (ZN) and bacterial culture. The search and data processing strategy is registered at PROSPERO (CRD42019123629). Medline via PubMed, EMBASE, Web of Science, and Cochrane Library databases were systematically searched for the keywords "pouched rat" and "tuberculosis". Data from 53,181 samples obtained from 24,600 patients were extracted from seven studies. Using sample-wise detection, the sensitivity of the studies was 86.7% [95% CI 80.4-91.2%], while the specificity was 88.4% [95% CI 79.7-93.7%]. For patient-wise detection, the sensitivity was 81.3% [95% CI 64.0-91.4%], while the specificity was 73.4% [95% CI 62.8-81.9%]. Good and excellent classification was assessed by hierarchical summary receiver-operating characteristic analysis for patient-wise and sample-wise detections, respectively. Our study is the first systematic review and meta-analysis of the above relatively inexpensive and rapid screening method. The results indicate that African giant pouched rats can discriminate healthy controls from TB individuals by sniffing sputum with even a higher accuracy than a single ZN screening.
Topics: Animals; Clinical Laboratory Techniques; Humans; Mycobacterium tuberculosis; Reproducibility of Results; Rodentia; Sensitivity and Specificity; Smell; Sputum; Tuberculosis, Pulmonary
PubMed: 33479276
DOI: 10.1038/s41598-021-81086-x -
BMC Infectious Diseases Mar 2017Efforts to control the global burden of tuberculosis (TB) have been jeopardized by the rapid evolution of multi-drug resistant Mycobacterium tuberculosis (MTB), which is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Efforts to control the global burden of tuberculosis (TB) have been jeopardized by the rapid evolution of multi-drug resistant Mycobacterium tuberculosis (MTB), which is resistant to at least isoniazid and rifampicin. Previous studies have documented variable prevalences of multidrug-resistant tuberculosis (MDR-TB) and its risk factors in Ethiopia. Therefore, this meta-analysis is aimed, firstly, to determine the pooled prevalence of MDR-TB among newly diagnosed and previously treated TB cases, and secondly, to measure the association between MDR-TB and a history of previous anti-TB drugs treatment.
METHODS
PubMed, Embase and Google Scholar databases were searched. Studies that reported a prevalence of MDR-TB among new and previously treated TB patients were selected. Studies or surveys conducted at national or sub-national level, with reported MDR-TB prevalence or sufficient data to calculate prevalence were considered for the analysis. Two authors searched and reviewed the studies for eligibility and extracted the data in pre-defined forms. Forest plots of all prevalence estimates were performed and summary estimates were also calculated using random effects models. Associations between previous TB treatment and MDR-MTB infection were examined through subgroup analyses stratified by new and previously treated patients.
RESULTS
We identified 16 suitable studies and found an overall prevalence of MDR-TB among newly diagnosed and previously treated TB patients to be 2% (95% CI 1% - 2%) and 15% (95% CI 12% - 17%), respectively. The observed difference was statistically significant (P < 0.001) and there was an odds ratio of 8.1 (95% CI 7.5-8.7) for previously treated TB patients to develop a MDR-MTB infection compared to newly diagnosed cases. For the past 10 years (2006 to 2014) the overall MDR-TB prevalence showed a stable time trend.
CONCLUSIONS
The burden of MDR-TB remains high in Ethiopian settings, especially in previously treated TB cases. Previous TB treatment was the most powerful predictor for MDR-MTB infection. Strict compliance with anti-TB regimens and improving case detection rate are the necessary steps to tackle the problem in Ethiopia.
Topics: Antitubercular Agents; Ethiopia; Humans; Isoniazid; Mycobacterium tuberculosis; Prevalence; Rifampin; Risk Factors; Tuberculosis, Multidrug-Resistant
PubMed: 28320336
DOI: 10.1186/s12879-017-2323-y -
Journal of Dairy Science Feb 2016Bovine paratuberculosis is a disease characterized by chronic granulomatous enteritis causing protein-losing enteropathy. Adverse effects on animal productivity are key... (Meta-Analysis)
Meta-Analysis Review
Bovine paratuberculosis is a disease characterized by chronic granulomatous enteritis causing protein-losing enteropathy. Adverse effects on animal productivity are key drivers in the attempt to control paratuberculosis at the farm level. Economic models require an accurate estimation of the production effects associated with paratuberculosis. The aim of this study was to conduct a systematic review and meta-analysis to investigate the effect of paratuberculosis on milk production. A total of 20 effect estimates from 15 studies were included in the final meta-analysis. Substantial between-study heterogeneity was observed. Subgroup analysis by case definition and study design was carried out to investigate heterogeneity. The majority of between-study variation was attributed to studies that defined cases on serology. Calculation of a pooled effect estimate was only appropriate for studies that defined cases by organism detection. A reduction in milk yield, corrected for lactation number and herd of origin of 1.87 kg/d, equivalent to 5.9% of yield, was associated with fecal culture or PCR positivity in individual cows.
Topics: Animals; Cattle; Cattle Diseases; Feces; Female; Lactation; Milk; Mycobacterium avium subsp. paratuberculosis; Paratuberculosis
PubMed: 26686704
DOI: 10.3168/jds.2015-10156 -
Antimicrobial Agents and Chemotherapy Oct 2011Standard culture-based testing of the susceptibility of Mycobacterium tuberculosis to pyrazinamide is difficult to perform. This systematic review with meta-analyses... (Meta-Analysis)
Meta-Analysis Review
Standard culture-based testing of the susceptibility of Mycobacterium tuberculosis to pyrazinamide is difficult to perform. This systematic review with meta-analyses evaluated the roles of molecular assays targeting pncA and of pyrazinamidase assays. PubMed and Embase were searched for relevant publications in English. Sensitivity and specificity were estimated in bivariate random-effects models. Of 128 articles identified, 73 sets of data involving culture isolates were initially included in meta-analyses. Summary estimates of sensitivity and specificity, respectively, were 87% and 93% for PCR-DNA sequencing (n = 29), 75% and 95% for PCR-single-stranded conformation polymorphism (SSCP) (n = 5), 96% and 97% for a mixture of other molecular assays (n = 6), and 89% and 97% for pyrazinamidase assays using the Wayne method (n = 33). The median prevalence (range) of pyrazinamide resistance was 51% (31% to 89%) in multidrug-resistant M. tuberculosis isolates and 5% (0% to 9%) in non-multidrug-resistant isolates. Excluding studies with possibly considerable false resistance in the reference assay gave the following estimates of sensitivity and specificity, respectively: 92% and 93% for PCR-DNA sequencing (n = 20), 98% and 96% for other molecular assays (n = 5), and 91% and 97% for the Wayne assay (n = 27). The Wayne assay had significant funnel plot asymmetry, so the test performance might have been overestimated. Considering the prevalence of pyrazinamide resistance in different clinical settings, PCR-DNA sequencing, and possibly other molecular assays targeting pncA, can detect pyrazinamide resistance in multidrug-resistant M. tuberculosis isolates, with predictive values largely exceeding 90%, and rule out pyrazinamide resistance in non-multidrug-resistant isolates, with predictive values exceeding 99%. Molecular assays are probably the way forward for detecting pyrazinamide resistance.
Topics: Amidohydrolases; Antitubercular Agents; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Polymerase Chain Reaction; Pyrazinamide; Sequence Analysis, DNA
PubMed: 21768515
DOI: 10.1128/AAC.00630-11 -
Clinical and Vaccine Immunology : CVI Oct 2011Tests that detect Mycobacterium tuberculosis antigens in clinical specimens could provide rapid direct evidence of active disease. We performed a systematic review to... (Meta-Analysis)
Meta-Analysis Review
Tests that detect Mycobacterium tuberculosis antigens in clinical specimens could provide rapid direct evidence of active disease. We performed a systematic review to assess the diagnostic accuracy of antigen detection tests for active tuberculosis (TB) according to standard methods and summarized test performance using bivariate random effects meta-analysis. Overall, study quality was a concern. For pulmonary TB (47 studies, 5,036 participants), sensitivity estimates ranged from 2% to 100% and specificity from 33% to 100%. Lipoarabinomannan (LAM) was the antigen most frequently targeted (23 studies, 49%). The pooled sensitivity of urine LAM was higher in HIV-infected than HIV-uninfected individuals (47%; 95% confidence interval [CI], 26 to 68% versus 14%; 95% CI, 4 to 38%); pooled specificity estimates were similar: 96%; 95% CI, 81 to 100% and 97%; 95% CI, 86 to 100%, respectively. For extrapulmonary TB (21 studies, 1,616 participants), sensitivity estimates ranged from 0% to 100% and specificity estimates from 62% to 100%. Five studies targeting LAM, ESAT-6, Ag85 complex, and the 65-kDa antigen in cerebrospinal fluid, when pooled, yielded the highest sensitivity (87%; 95% CI, 61 to 98%), but low specificity (84%; 95% CI, 60 to 95%). Because of the limited number of studies targeting any specific antigen other than LAM, we could not draw firm conclusions about the overall clinical usefulness of these tests. Further studies are warranted to determine the value of LAM detection for TB meningitis in high-HIV-prevalence settings. Considering that antigen detection tests could be translated into rapid point-of-care tests, research to improve their performance is urgently needed.
Topics: Antigens, Bacterial; Clinical Laboratory Techniques; Humans; Immunoassay; Mycobacterium tuberculosis; Sensitivity and Specificity; Tuberculosis
PubMed: 21832100
DOI: 10.1128/CVI.05205-11 -
PLoS Medicine Aug 2011Serological (antibody detection) tests for tuberculosis (TB) are widely used in developing countries. As part of a World Health Organization policy process, we performed... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Serological (antibody detection) tests for tuberculosis (TB) are widely used in developing countries. As part of a World Health Organization policy process, we performed an updated systematic review to assess the diagnostic accuracy of commercial serological tests for pulmonary and extrapulmonary TB with a focus on the relevance of these tests in low- and middle-income countries.
METHODS AND FINDINGS
We used methods recommended by the Cochrane Collaboration and GRADE approach for rating quality of evidence. In a previous review, we searched multiple databases for papers published from 1 January 1990 to 30 May 2006, and in this update, we add additional papers published from that period until 29 June 2010. We prespecified subgroups to address heterogeneity and summarized test performance using bivariate random effects meta-analysis. For pulmonary TB, we included 67 studies (48% from low- and middle-income countries) with 5,147 participants. For all tests, estimates were variable for sensitivity (0% to 100%) and specificity (31% to 100%). For anda-TB IgG, the only test with enough studies for meta-analysis, pooled sensitivity was 76% (95% CI 63%-87%) in smear-positive (seven studies) and 59% (95% CI 10%-96%) in smear-negative (four studies) patients; pooled specificities were 92% (95% CI 74%-98%) and 91% (95% CI 79%-96%), respectively. Compared with ELISA (pooled sensitivity 60% [95% CI 6%-65%]; pooled specificity 98% [95% CI 96%-99%]), immunochromatographic tests yielded lower pooled sensitivity (53%, 95% CI 42%-64%) and comparable pooled specificity (98%, 95% CI 94%-99%). For extrapulmonary TB, we included 25 studies (40% from low- and middle-income countries) with 1,809 participants. For all tests, estimates were variable for sensitivity (0% to 100%) and specificity (59% to 100%). Overall, quality of evidence was graded very low for studies of pulmonary and extrapulmonary TB.
CONCLUSIONS
Despite expansion of the literature since 2006, commercial serological tests continue to produce inconsistent and imprecise estimates of sensitivity and specificity. Quality of evidence remains very low. These data informed a recently published World Health Organization policy statement against serological tests. Please see later in the article for the Editors' Summary.
Topics: Antibodies, Bacterial; Antigens, Bacterial; Bias; Developing Countries; Enzyme-Linked Immunosorbent Assay; Humans; Mycobacterium tuberculosis; Sensitivity and Specificity; Serologic Tests; Tuberculosis; Tuberculosis, Pulmonary
PubMed: 21857806
DOI: 10.1371/journal.pmed.1001062 -
The Lancet. Global Health Aug 2017The performance of laboratory tests to diagnose pulmonary tuberculosis is dependent on the quality of the sputum sample tested. The relative merits of sputum collection... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
The performance of laboratory tests to diagnose pulmonary tuberculosis is dependent on the quality of the sputum sample tested. The relative merits of sputum collection methods to improve tuberculosis diagnosis are poorly characterised. We therefore aimed to investigate the effects of sputum collection methods on tuberculosis diagnosis.
METHODS
We did a systematic review and meta-analysis to investigate whether non-invasive sputum collection methods in people aged at least 12 years improve the diagnostic performance of laboratory testing for pulmonary tuberculosis. We searched PubMed, Google Scholar, ProQuest, Web of Science, CINAHL, and Embase up to April 14, 2017, to identify relevant experimental, case-control, or cohort studies. We analysed data by pairwise meta-analyses with a random-effects model and by network meta-analysis. All diagnostic performance data were calculated at the sputum-sample level, except where authors only reported data at the individual patient-level. Heterogeneity was assessed, with potential causes identified by logistic meta-regression.
FINDINGS
We identified 23 eligible studies published between 1959 and 2017, involving 8967 participants who provided 19 252 sputum samples. Brief, on-demand spot sputum collection was the main reference standard. Pooled sputum collection increased tuberculosis diagnosis by microscopy (odds ratio [OR] 1·6, 95% CI 1·3-1·9, p<0·0001) or culture (1·7, 1·2-2·4, p=0·01). Providing instructions to the patient before sputum collection, during observed collection, or together with physiotherapy assistance increased diagnostic performance by microscopy (OR 1·6, 95% CI 1·3-2·0, p<0·0001). Collecting early morning sputum did not significantly increase diagnostic performance of microscopy (OR 1·5, 95% CI 0·9-2·6, p=0·2) or culture (1·4, 0·9-2·4, p=0·2). Network meta-analysis confirmed these findings, and revealed that both pooled and instructed spot sputum collections were similarly effective techniques for increasing the diagnostic performance of microscopy.
INTERPRETATION
Tuberculosis diagnoses were substantially increased by either pooled collection or by providing instruction on how to produce a sputum sample taken at any time of the day. Both interventions had a similar effect to that reported for the introduction of new, expensive laboratory tests, and therefore warrant further exploration in the drive to end the global tuberculosis epidemic.
FUNDING
Wellcome Trust, Joint Global Health Trials consortium, Innovation For Health and Development, and Bill & Melinda Gates Foundation.
Topics: Humans; Microscopy; Mycobacterium tuberculosis; Network Meta-Analysis; Odds Ratio; Physical Therapy Modalities; Sensitivity and Specificity; Specimen Handling; Sputum; Time Factors; Tuberculosis, Pulmonary
PubMed: 28625793
DOI: 10.1016/S2214-109X(17)30201-2 -
The Cochrane Database of Systematic... Jan 2013Bacillus Calmette-Guerín (BCG) is a live attenuated vaccine to prevent tuberculosis, routinely administered at birth as part of the World Health Organization global... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bacillus Calmette-Guerín (BCG) is a live attenuated vaccine to prevent tuberculosis, routinely administered at birth as part of the World Health Organization global expanded immunisation programme. Given intradermally, it can cause adverse reactions, including local, regional, distant and disseminated manifestations that may cause parental distress. Rarely, it can cause serious illness and even death. Among those patients with immunocompromised conditions, such as the human immunodeficiency virus (HIV) infection, the complication rate is even higher.
OBJECTIVES
To assess the effects of different interventions for treating BCG-induced disease in children.
SEARCH METHODS
The following databases were searched: the Cochrane Infectious Diseases Group Specialized Register and Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library (The Cochrane Library 2012, Issue 4); MEDLINE (1966 to November 2012); EMBASE (1947 to November 2012); and LILACS (1980 to November 2012). The metaRegister of Controlled Trials (mRCT) and the WHO trials search portal. Conference proceedings for relevant abstracts and experts were also contacted to identify studies. No language restrictions were applied.
SELECTION CRITERIA
Randomized controlled trials (RCTs) comparing any medical or surgical treatment modality for BCG-induced disease in children.
DATA COLLECTION AND ANALYSIS
Two authors independently evaluated titles, applied inclusion criteria, and assessed the risk of bias of studies. The primary outcomes were the failure rate of therapies for all types of BCG vaccine-induced complications and the time to resolution of illness measured in months. The secondary outcomes were death from BCG vaccine-induced disease and the all-cause mortality. Risk ratios (RRs) were used as measure of effect for dichotomous outcomes and mean differences for continuous outcomes.
MAIN RESULTS
Five RCTs analysing 341 children addressed the primary outcomes and were included. Four arms compared oral antibiotics to no intervention or placebo, one arm evaluated needle aspiration compared to no intervention, and another evaluated the use of locally instilled isoniazid versus oral erythromycin.Two small studies evaluated oral isoniazid; we are uncertain of whether this intervention has an effect on clinical failure (RR 1.48; 95% Confidence Interval (CI) 0.79 to 2.78; 54 participants, two studies, very low quality evidence). Similarly, for oral erythromycin, we are uncertain if there is an effect (clinical failure RR 1.03; 95% CI 0.70 to 1.53; 148 participants, three studies, very low quality evidence), and for oral isoniazid plus rifampicin (clinical failure, RR 1.20; 95% CI 0.51 to 2.83; 35 participants, one study, very low quality evidence).In patients with lymphadenitis abscess, needle aspiration may reduce clinically persistent BCG-induced disease at 6 to 9 months of follow-up (RR 0.13; 95% CI 0.03 to 0.55; 77 participants, one study, low quality evidence). In another study of patients with the same condition, aspiration plus local instillation of isoniazid reduces time to clinical cure compared to aspiration plus oral erythromycin (mean difference 1.49 months less; 95% CI 0.82 to 2.15 less; 27 participants, one study).No RCTs of HIV-infected infants with a BCG-induced disease evaluated the use of antibiotics or other therapies for reducing the rate of clinical failure or the time to clinical resolution. No data on mortality secondary to the interventions for treating BCG-induced disease were reported.
AUTHORS' CONCLUSIONS
It is unclear if oral antibiotics (isoniazid, erythromycin, or a combination of isoniazid plus rifampicin) are effective for the resolution of BCG-induced disease. Most non-suppurated lymphadenitis will resolve without treatment in 4 to 6 months. Patients with lymphadenitis abscess might benefit from needle aspiration and possibly local instillation of isoniazid could shorten recovery time. Included studies were generally small and could be better conducted. Further research should evaluate the use of needle aspiration and local instillation of isoniazid in fluctuant nodes. Therapeutic and preventive measures in HIV-infected infants could be important given the higher risk of negative outcomes in this group.
Topics: Abscess; Adjuvants, Immunologic; Antibiotics, Antitubercular; BCG Vaccine; Child; Child, Preschool; Erythromycin; Humans; Infant; Isoniazid; Lymphadenitis; Mycobacterium bovis; Randomized Controlled Trials as Topic; Rifampin; Suction
PubMed: 23440826
DOI: 10.1002/14651858.CD008300.pub2 -
The European Respiratory Journal Mar 2014Treatment of multidrug-resistant (MDR) tuberculosis (TB) is challenging because of the high toxicity of second-line drugs and the longer treatment duration than for... (Review)
Review
Treatment of multidrug-resistant (MDR) tuberculosis (TB) is challenging because of the high toxicity of second-line drugs and the longer treatment duration than for drug-susceptible TB patients. In order to speed up novel treatment for MDR-TB, we suggest considering expanding the indications of already available drugs. Six drugs with antimicrobial activity (phenothiazine, metronidazole, doxycycline, disulfiram, tigecycline and co-trimoxazole) are not listed in the World Health Organization guidelines on MDR-TB treatment but could be potential candidates for evaluation against Mycobacterium tuberculosis. A systematic review was conducted to evaluate antituberculous activity of these drugs against M. tuberculosis. We searched PubMed, Google Scholar and Embase for English articles published up to December 31, 2012. We reviewed in vitro, in vivo and clinical antituberculous activity of these drugs in addition to pharmacokinetics and side-effects. Of the drugs effective against actively replicating M. tuberculosis, co-trimoxazole seems to be the most promising, because of its consistent pharmacokinetic profile, easy penetration into tissue and safety profile. For the dormant state of TB, thioridazine may play a potential role as an adjuvant for treatment of MDR-TB. A strategy consisting of pharmacokinetic/pharmacodynamic studies, dose finding and phase III studies is needed to explore the role of these drugs in MDR-TB treatment.
Topics: Anti-Infective Agents; Antitubercular Agents; Chemistry, Pharmaceutical; Clinical Trials as Topic; Disulfiram; Doxycycline; Drug Design; Humans; Metronidazole; Minocycline; Mycobacterium tuberculosis; Phenothiazines; Tigecycline; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Multidrug-Resistant
PubMed: 23988774
DOI: 10.1183/09031936.00113713 -
Scientific Reports Mar 2018Little is known about the impact of comorbidities on multidrug resistant (MDR) and extensively drug resistant (XDR) tuberculosis (TB) treatment outcomes. We aimed to... (Meta-Analysis)
Meta-Analysis
Little is known about the impact of comorbidities on multidrug resistant (MDR) and extensively drug resistant (XDR) tuberculosis (TB) treatment outcomes. We aimed to examine the effect of human immunodeficiency virus (HIV), diabetes, chronic kidney disease (CKD), alcohol misuse, and smoking on MDR/XDRTB treatment outcomes. We searched MEDLINE, EMBASE, Cochrane Central Registrar and Cochrane Database of Systematic Reviews as per PRISMA guidelines. Eligible studies were identified and treatment outcome data were extracted. We performed a meta-analysis to generate a pooled relative risk (RR) for unsuccessful outcome in MDR/XDRTB treatment by co-morbidity. From 2457 studies identified, 48 reported on 18,257 participants, which were included in the final analysis. Median study population was 235 (range 60-1768). Pooled RR of unsuccessful outcome was higher in people living with HIV (RR = 1.41 [95%CI: 1.15-1.73]) and in people with alcohol misuse (RR = 1.45 [95%CI: 1.21-1.74]). Outcomes were similar in people with diabetes or in people that smoked. Data was insufficient to examine outcomes in exclusive XDRTB or CKD cohorts. In this systematic review and meta-analysis, alcohol misuse and HIV were associated with higher pooled OR of an unsuccessful outcome in MDR/XDRTB treatment. Further research is required to understand the role of comorbidities in driving unsuccessful treatment outcomes.
Topics: Alcoholism; Antitubercular Agents; Comorbidity; Diabetes Mellitus; Drug Resistance, Multiple, Bacterial; HIV Infections; Humans; Mycobacterium tuberculosis; Renal Insufficiency, Chronic; Smoking; Treatment Outcome; Tuberculosis, Multidrug-Resistant
PubMed: 29563561
DOI: 10.1038/s41598-018-23344-z