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1.
Neeraj Raizada Kuldeep Singh Sachdeva Sreenivas Achuthan Nair Shubhangi Kulsange Radhey Shayam Gupta Rahul Thakur Malik Parmar Christen Gray Ranjani Ramachandran Bhavin Vadera Shobha Ekka Shikha Dhawan Ameet Babre Mayank Ghedia Umesh Alavadi Puneet Dewan Mini Khetrapal Ashwini Khanna Catharina Boehme Chinnambedu Nainarappan Paramsivan 《PloS one》2014,9(8)
Background
Diagnosis of pulmonary tuberculosis (PTB) in children is challenging due to difficulties in obtaining good quality sputum specimens as well as the paucibacillary nature of disease. Globally a large proportion of pediatric tuberculosis (TB) cases are diagnosed based only on clinical findings. Xpert MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution in addressing these challenges. This study presents the results from pediatric groups taking part in a large demonstration study wherein Xpert MTB/RIF testing replaced smear microscopy for all presumptive PTB cases in public health facilities across India.Methods
The study covered a population of 8.8 million across 18 programmatic sub-district level tuberculosis units (TU), with one Xpert MTB/RIF platform established at each study TU. Pediatric presumptive PTB cases (both TB and Drug Resistant TB (DR-TB)) accessing any public health facilities in study area were prospectively enrolled and tested on Xpert MTB/RIF following a standardized diagnostic algorithm.Results
4,600 pediatric presumptive pulmonary TB cases were enrolled. 590 (12.8%, CI 11.8–13.8) pediatric PTB were diagnosed. Overall 10.4% (CI 9.5–11.2) of presumptive PTB cases had positive results by Xpert MTB/RIF, compared with 4.8% (CI 4.2–5.4) who had smear-positive results. Upfront Xpert MTB/RIF testing of presumptive PTB and presumptive DR-TB cases resulted in diagnosis of 79 and 12 rifampicin resistance cases, respectively. Positive predictive value (PPV) for rifampicin resistance detection was high (98%, CI 90.1–99.9), with no statistically significant variation with respect to past history of treatment.Conclusion
Upfront access to Xpert MTB/RIF testing in pediatric presumptive PTB cases was associated with a two-fold increase in bacteriologically-confirmed PTB, and increased detection of rifampicin-resistant TB cases under routine operational conditions across India. These results suggest that routine Xpert MTB/RIF testing is a promising solution to present-day challenges in the diagnosis of PTB in pediatric patients. 相似文献2.
Sanne C. van Kampen Nugroho H. Susanto Sumanto Simon Shinta D. Astiti Roni Chandra Erlina Burhan Muhammad N. Farid Kendra Chittenden Dyah E. Mustikawati Bachti Alisjahbana 《PloS one》2015,10(6)
Background
In March 2012, the Xpert MTB/RIF assay (Xpert) was introduced in three provincial public hospitals in Indonesia as a novel diagnostic to detect tuberculosis and rifampicin resistance among high risk individuals.Objective
This study assessed the effects of using Xpert in place of conventional solid and liquid culture and drug-susceptibility testing on case detection rates, treatment initiation rates, and health system delays among drug-resistant tuberculosis (TB) patients.Methods
Cohort data on registration, test results and treatment initiation were collected from routine presumptive patient registers one year before and one year after Xpert was introduced. Proportions of case detection and treatment initiation were compared using the Pearson Chi square test and median time delays using the Mood’s Median test.Results
A total of 975 individuals at risk of drug-resistant TB were registered in the pre-intervention year and 1,442 in the post-intervention year. After Xpert introduction, TB positivity rate increased by 15%, while rifampicin resistance rate reduced by 23% among TB positive cases and by 9% among all tested. Second-line TB treatment initiation rate among rifampicin resistant patients increased by 19%. Time from client registration to diagnosis was reduced by 74 days to a median of a single day (IQR 0–4) and time from diagnosis to treatment start was reduced by 27 days to a median of 15 days (IQR 7–51). All findings were significant with p<0.001.Conclusion
Compared to solid and liquid culture and drug-susceptibility testing, Xpert detected more TB and less rifampicin resistance, increased second-line treatment initiation rates and shortened time to diagnosis and treatment. This test holds promise to improve rapid case finding and management of drug-resistant TB patients in Indonesia. 相似文献3.
Violet N. Chihota Sibuse Ginindza Kerrigan McCarthy Alison D. Grant Gavin Churchyard Katherine Fielding 《PloS one》2015,10(9)
Setting
40 primary health clinics (PHCs) in four provinces in South Africa, June 2012 –February 2013.Objective
To determine whether health care worker (HCW) practice in investigating people with TB symptoms was altered when the initial test for TB was changed from smear microscopy to Xpert MTB/RIF.Design
Cross-sectional substudy at clinics participating in a pragmatic cluster randomised trial, Xpert for TB: Evaluating a New Diagnostic "XTEND", which evaluated the effect of Xpert MTB/RIF implementation in South Africa.Methods
Consecutive adults exiting PHCs reporting at least one TB symptom (defined as any of cough, weight loss, night sweats and fever) were enrolled. The main outcome was the proportion who self-reported having sputum requested by HCW during the clinic encounter just completed.Results
3604 adults exiting PHCs (1676 in Xpert arm, 1928 in microscopy arm) were enrolled (median age 38 years, 71.4% female, 38.8% reported being HIV-positive, 70% reported cough). For 1267 participants (35.2%) the main reason for attending the clinic was TB symptom(s).Overall 2130/3604 (59.1%) said they reported their symptom(s) to HCW. 22.7% (818/3604) reported having been asked to give sputum for TB investigation. Though participants in the Xpert vs. microscopy arm were more likely to have sputum requested by HCW, this was not significantly different: overall (26.0% [436/1676] vs 19.8% [382/1928]; adjusted prevalence ratio [aPR] 1.31, [95% CI 0.78–2.20]) and when restricted to those presenting at clinics due to symptoms (49.1% [260/530] vs 29.9% [220/737]; aPR 1.38 [0.89–2.13]) and those reporting being HIV-positive (29.4% [190/647] vs 20.8% [156/749]; aPR 1.38[0.88–2.16]).Those attending clinic due to TB symptoms, were more likely to have sputum requested if they had increasing number of symptoms; longer duration of cough, unintentional weight loss and night sweats and if they reported symptoms to HCW.Conclusions
A large proportion of people exiting PHCs reporting TB symptoms did not get tested. Implementation of Xpert MTB/RIF did not substantially change the probability of testing for TB. Better systems are needed to ensure that opportunities to identify active TB among PHC attendees are not missed. 相似文献4.
Elisa Ardizzoni Emmanuel Fajardo Peter Saranchuk Martina Casenghi Anne-Laure Page Francis Varaine Cara S. Kosack Pamela Hepple 《PloS one》2015,10(12)
Background
The Xpert® MTB/RIF (Xpert) is an automated molecular test for simultaneous detection of tuberculosis (TB) and rifampicin resistance, recommended by the World Health Organization as the preferred diagnostic method for individuals presumed to have multi-drug resistant TB (MDR-TB) or HIV-associated TB. We describe the performance of Xpert and key lessons learned during two years of implementation under routine conditions in 33 projects located in 18 countries supported by Médecins Sans Frontières across varied geographic, epidemiological and clinical settings.Methods
Xpert was used following three strategies: the first being as the initial test, with microscopy in parallel, for all presumptive TB cases; the second being only for patients at risk of MDR-TB, or with HIV- associated TB, or presumptive paediatric TB; and the third being as the initial test for these high-risk patients plus as an add-on test to microscopy in others. Routine laboratory data were collected, using laboratory registers. Qualitative data such as logistic aspects, human resources, and tool acceptance were collected using a questionnaire.Findings
In total, 52,863 samples underwent Xpert testing from April 2011 to December 2012. The average MTB detection rate was 18.5%, 22.3%, and 11.6% for the three different strategies respectively. Analysis of the results on samples tested in parallel showed that using Xpert as add-on test to microscopy would have increased laboratory TB confirmation by 49.7%, versus 42.3% for Xpert replacing microscopy. The main limitation of the test was the high rate of inconclusive results, which correlated with factors such as defective modules, cartridge version (G3 vs. G4) and staff experience. Operational and logistical hurdles included infrastructure renovation, basic computer training, regular instrument troubleshooting and maintenance, all of which required substantial and continuous support.Conclusion
The implementation of Xpert was feasible and significantly increased TB detection compared to microscopy, despite the high rate of inconclusive results. Xpert implementation was accompanied by considerable operational and logistical challenges. To further decentralize diagnosis, simpler, low-cost TB technologies well-suited to low-resource settings are still urgently needed. 相似文献5.
David W. Dowdy J. Lucian Davis Saskia den Boon Nicholas D. Walter Achilles Katamba Adithya Cattamanchi 《PloS one》2013,8(8)
Objective
To compare the population-level impact of two World Health Organization-endorsed strategies for improving the diagnosis of tuberculosis (TB): same-day microscopy and Xpert MTB/RIF (Cepheid, USA).Methods
We created a compartmental transmission model of TB in a representative African community, fit to the regional incidence and mortality of TB and HIV. We compared the population-level reduction in TB burden over ten years achievable with implementation over two years of same-day microscopy, Xpert MTB/RIF testing, and the combination of both approaches.Findings
Same-day microscopy averted an estimated 11.0% of TB incidence over ten years (95% uncertainty range, UR: 3.3%–22.5%), and prevented 11.8% of all TB deaths (95% UR: 7.7%–27.1%). Scaling up Xpert MTB/RIF to all centralized laboratories to achieve 75% population coverage had similar impact on incidence (9.3% reduction, 95% UR: 1.9%–21.5%) and greater effect on mortality (23.8% reduction, 95% UR: 8.6%–33.4%). Combining the two strategies (i.e., same-day microscopy plus Xpert MTB/RIF) generated synergistic effects: an 18.7% reduction in incidence (95% UR: 5.6%–39.2%) and 33.1% reduction in TB mortality (95% UR: 18.1%–50.2%). By the end of year ten, combining same-day microscopy and Xpert MTB/RIF could reduce annual TB mortality by 44% relative to the current standard of care.Conclusion
Scaling up novel diagnostic tests for TB and optimizing existing ones are complementary strategies that, when combined, may have substantial impact on TB epidemics in Africa. 相似文献6.
Christina Yoon Adithya Cattamanchi J. Lucian Davis William Worodria Saskia den Boon Nelson Kalema Winceslaus Katagira Sylvia Kaswabuli Cecily Miller Alfred Andama Heidi Albert Pamela Nabeta Christen Gray Irene Ayakaka Laurence Huang 《PloS one》2012,7(11)
Rationale
The clinical impact of Xpert MTB/RIF for tuberculosis (TB) diagnosis in high HIV-prevalence settings is unknown.Objective
To determine the diagnostic accuracy and impact of Xpert MTB/RIF among high-risk TB suspects.Methods
We prospectively enrolled consecutive, hospitalized, Ugandan TB suspects in two phases: baseline phase in which Xpert MTB/RIF results were not reported to clinicians and an implementation phase in which results were reported. We determined the diagnostic accuracy of Xpert MTB/RIF in reference to culture (solid and liquid) and compared patient outcomes by study phase.Results
477 patients were included (baseline phase 287, implementation phase 190). Xpert MTB/RIF had high sensitivity (187/237, 79%, 95% CI: 73–84%) and specificity (190/199, 96%, 95% CI: 92–98%) for culture-positive TB overall, but sensitivity was lower (34/81, 42%, 95% CI: 31–54%) among smear-negative TB cases. Xpert MTB/RIF reduced median days-to-TB detection for all TB cases (1 [IQR 0–26] vs. 0 [IQR 0–1], p<0.001), and for smear-negative TB (35 [IQR 22–55] vs. 22 [IQR 0–33], p = 0.001). However, median days-to-TB treatment was similar for all TB cases (1 [IQR 0–5] vs. 0 [IQR 0–2], p = 0.06) and for smear-negative TB (7 [IQR 3–53] vs. 6 [IQR 1–61], p = 0.78). Two-month mortality was also similar between study phases among 252 TB cases (17% vs. 14%, difference +3%, 95% CI: −21% to +27%, p = 0.80), and among 87 smear-negative TB cases (28% vs. 22%, difference +6%, 95% CI: −34 to +46%, p = 0.77).Conclusions
Xpert MTB/RIF facilitated more accurate and earlier TB diagnosis, leading to a higher proportion of TB suspects with a confirmed TB diagnosis prior to hospital discharge in a high HIV/low MDR TB prevalence setting. However, our study did not detect a decrease in two-month mortality following implementation of Xpert MTB/RIF possibly because of insufficient powering, differences in empiric TB treatment rates, and disease severity between study phases. 相似文献7.
Erick Wekesa Bunyasi Michele Tameris Hennie Geldenhuys Bey-Marrie Schmidt Angelique Kany Kany Luabeya Humphrey Mulenga Thomas J. Scriba Willem A. Hanekom Hassan Mahomed Helen McShane Mark Hatherill 《PloS one》2015,10(11)
Objective
Diagnosis of childhood tuberculosis is limited by the paucibacillary respiratory samples obtained from young children with pulmonary disease. We aimed to compare accuracy of the Xpert® MTB/RIF assay, an automated nucleic acid amplification test, between induced sputum and gastric lavage samples from young children in a tuberculosis endemic setting.Methods
We analyzed standardized diagnostic data from HIV negative children younger than four years of age who were investigated for tuberculosis disease near Cape Town, South Africa [2009–2012]. Two paired, consecutive induced sputa and early morning gastric lavage samples were obtained from children with suspected tuberculosis. Samples underwent Mycobacterial Growth Indicator Tube [MGIT] culture and Xpert MTB/RIF assay. We compared diagnostic yield across samples using the two-sample test of proportions and McNemar’s χ2 test; and Wilson’s score method to calculate sensitivity and specificity.Results
1,020 children were evaluated for tuberculosis during 1,214 admission episodes. Not all children had 4 samples collected. 57 of 4,463[1.3%] and 26 of 4,606[0.6%] samples tested positive for Mycobacterium tuberculosis on MGIT culture and Xpert MTB/RIF assay respectively. 27 of 2,198[1.2%] and 40 of 2,183[1.8%] samples tested positive [on either Xpert MTB/RIF assay or MGIT culture] on induced sputum and gastric lavage samples, respectively. 19/1,028[1.8%] and 33/1,017[3.2%] admission episodes yielded a positive MGIT culture or Xpert MTB/RIF assay from induced sputum and gastric lavage, respectively. Sensitivity of Xpert MTB/RIF assay was 8/30[26.7%; 95% CI: 14.2–44.4] for two induced sputum samples and 7/31[22.6%; 11.4–39.8] [p = 0.711] for two gastric lavage samples. Corresponding specificity was 893/893[100%;99.6–100] and 885/890[99.4%;98.7–99.8] respectively [p = 0.025].Conclusion
Sensitivity of Xpert MTB/RIF assay was low, compared to MGIT culture, but diagnostic performance of Xpert MTB/RIF did not differ sufficiently between induced sputum and gastric lavage to justify selection of one sampling method over the other, in young children with suspected pulmonary TB.Trial Registration
ClinicalTrials.gov NCT00953927 相似文献8.
Mai T. Pho Sarang Deo Kara M. Palamountain Moses Lutaakome Joloba Francis Bajunirwe Achilles Katamba 《PloS one》2015,10(4)
Background
Xpert MTB/RIF (Xpert) is being widely adopted in high TB burden countries. Analysis is needed to guide the placement of devices within health systems to optimize the tuberculosis (TB) case detection rate (CDR).Methods
We used epidemiological and operational data from Uganda (139 sites serving 87,600 individuals tested for TB) to perform a model-based comparison of the following placement strategies for Xpert devices: 1) Health center level (sites ranked by size from national referral hospitals to health care level III centers), 2) Smear volume (sites ranked from highest to lowest volume of smear microscopy testing), 3) Antiretroviral therapy (ART) volume (sites ranked from greatest to least patients on ART), 4) External equality assessment (EQA) performance (sites ranked from worst to best smear microscopy performance) and 5) TB prevalence (sites ranked from highest to lowest). We compared two clinical algorithms, one where Xpert was used only for smear microscopy negative samples versus another replacing smear microscopy. The primary outcome was TB CDR; secondary outcomes were detection of multi-drug resistant TB, number of sites requiring device placement to achieve specified rollout coverage, and cost.Results
Placement strategies that prioritized sites with higher TB prevalence maximized CDR, with an incremental rate of 6.2–12.6% compared to status quo (microscopy alone). Diagnosis of MDR-TB was greatest in the TB Prevalence strategy when Xpert was used in place of smear microscopy. While initial implementation costs were lowest in the Smear Volume strategy, cost per additional TB case detected was lowest in the TB prevalence strategy.Conclusion
In Uganda, placement of Xpert devices in sites with high TB prevalence yielded the highest TB CDR at the lowest cost per additional case diagnosed. These results represent novel use of program level data to inform the optimal placement of new technology in resource-constrained settings. 相似文献9.
Lawn SD Brooks SV Kranzer K Nicol MP Whitelaw A Vogt M Bekker LG Wood R 《PLoS medicine》2011,8(7):e1001067
Background
The World Health Organization has endorsed the Xpert MTB/RIF assay for investigation of patients suspected of having tuberculosis (TB). However, its utility for routine TB screening and detection of rifampicin resistance among HIV-infected patients with advanced immunodeficiency enrolling in antiretroviral therapy (ART) services is unknown.Methods and Findings
Consecutive adult HIV-infected patients with no current TB diagnosis enrolling in an ART clinic in a South African township were recruited regardless of symptoms. They were clinically characterised and invited to provide two sputum samples at a single visit. The accuracy of the Xpert MTB/RIF assay for diagnosing TB and drug resistance was assessed in comparison with other tests, including fluorescence smear microscopy and automated liquid culture (gold standard) and drug susceptibility testing. Of 515 patients enrolled, 468 patients (median CD4 cell count, 171 cells/µl; interquartile range, 102–236) produced at least one sputum sample, yielding complete sets of results from 839 samples. Mycobacterium tuberculosis was cultured from 81 patients (TB prevalence, 17.3%). The overall sensitivity of the Xpert MTB/RIF assay for culture-positive TB was 73.3% (specificity, 99.2%) compared to 28.0% (specificity, 100%) using smear microscopy. All smear-positive, culture-positive disease was detected by Xpert MTB/RIF from a single sample (sensitivity, 100%), whereas the sensitivity for smear-negative, culture-positive TB was 43.4% from one sputum sample and 62.3% from two samples. Xpert correctly identified rifampicin resistance in all four cases of multidrug-resistant TB but incorrectly identified resistance in three other patients whose disease was confirmed to be drug sensitive by gene sequencing (specificity, 94.1%; positive predictive value, 57%).Conclusions
In this population of individuals at high risk of TB, intensive screening using the Xpert MTB/RIF assay increased case detection by 45% compared with smear microscopy, strongly supporting replacement of microscopy for this indication. However, despite the ability of the assay to rapidly detect rifampicin-resistant disease, the specificity for drug-resistant TB was sub-optimal. Please see later in the article for the Editors'' Summary 相似文献10.
Scott LE McCarthy K Gous N Nduna M Van Rie A Sanne I Venter WF Duse A Stevens W 《PLoS medicine》2011,8(7):e1001061
Background
The Xpert MTB/RIF (Cepheid) non-laboratory-based molecular assay has potential to improve the diagnosis of tuberculosis (TB), especially in HIV-infected populations, through increased sensitivity, reduced turnaround time (2 h), and immediate identification of rifampicin (RIF) resistance. In a prospective clinical validation study we compared the performance of Xpert MTB/RIF, MTBDRplus (Hain Lifescience), LightCycler Mycobacterium Detection (LCTB) (Roche), with acid fast bacilli (AFB) smear microscopy and liquid culture on a single sputum specimen.Methods and Findings
Consecutive adults with suspected TB attending a primary health care clinic in Johannesburg, South Africa, were prospectively enrolled and evaluated for TB according to the guidelines of the National TB Control Programme, including assessment for smear-negative TB by chest X-ray, clinical evaluation, and HIV testing. A single sputum sample underwent routine decontamination, AFB smear microscopy, liquid culture, and phenotypic drug susceptibility testing. Residual sample was batched for molecular testing. For the 311 participants, the HIV prevalence was 70% (n = 215), with 120 (38.5%) culture-positive TB cases. Compared to liquid culture, the sensitivities of all the test methodologies, determined with a limited and potentially underpowered sample size (n = 177), were 59% (47%–71%) for smear microscopy, 76% (64%–85%) for MTBDRplus, 76% (64%–85%) for LCTB, and 86% (76%–93%) for Xpert MTB/RIF, with specificities all >97%. Among HIV+ individuals, the sensitivity of the Xpert MTB/RIF test was 84% (69%–93%), while the other molecular tests had sensitivities reduced by 6%. TB detection among smear-negative, culture-positive samples was 28% (5/18) for MTBDRplus, 22% (4/18) for LCTB, and 61% (11/18) for Xpert MTB/RIF. A few (n = 5) RIF-resistant cases were detected using the phenotypic drug susceptibility testing methodology. Xpert MTB/RIF detected four of these five cases (fifth case not tested) and two additional phenotypically sensitive cases.Conclusions
The Xpert MTB/RIF test has superior performance for rapid diagnosis of Mycobacterium tuberculosis over existing AFB smear microscopy and other molecular methodologies in an HIV- and TB-endemic region. Its place in the clinical diagnostic algorithm in national health programs needs exploration. Please see later in the article for the Editors'' Summary 相似文献11.
Background
Multidrug-resistant tuberculosis (MDR-TB) is resistant to both rifampicin (RIF) and isoniazid (INH). Whereas many TB diagnostics detect RIF-resistance, few detect INH-monoresistance, which is common and may increase risk of acquired MDR-TB. Whether inclusion of INH-resistance in a first-line rapid test for TB would have an important impact on MDR-TB rates remains uncertain.Methods
We developed a transmission model to evaluate three tests in a population similar to that of India: a rapid molecular test for TB, the same test plus RIF-resistance detection (“TB+RIF”), and detection of RIF and INH-resistance (“TB+RIF/INH”). Our primary outcome was the prevalence of INH-resistant and MDR-TB at ten years.Results
Compared to the TB test alone and assuming treatment of all diagnosed MDR cases, the TB+RIF test reduced the prevalence of MDR-TB among all TB cases from 5.5% to 3.8% (30.6% reduction, 95% uncertainty range, UR: 17–54%). Despite using liberal assumptions about the impact of INH-monoresistance on treatment outcomes and MDR-TB acquisition, expansion from TB+RIF to TB+RIF/INH lowered this prevalence only from 3.8% to 3.6% further (4% reduction, 95% UR: 3–7%) and INH-monoresistant TB from 15.8% to 15.1% (4% reduction, 95% UR: (-8)-19%).Conclusion
When added to a rapid test for TB plus RIF-resistance, detection of INH-resistance has minimal impact on transmission of TB, MDR-TB, and INH-monoresistant TB. 相似文献12.
Background
The Xpert MTB/RIF test enables rapid detection of tuberculosis (TB) and rifampicin resistance. The World Health Organization recommends Xpert for initial diagnosis in individuals suspected of having multidrug-resistant TB (MDR-TB) or HIV-associated TB, and many countries are moving quickly toward adopting Xpert. As roll-out proceeds, it is essential to understand the potential health impact and cost-effectiveness of diagnostic strategies based on Xpert.Methods and Findings
We evaluated potential health and economic consequences of implementing Xpert in five southern African countries—Botswana, Lesotho, Namibia, South Africa, and Swaziland—where drug resistance and TB-HIV coinfection are prevalent. Using a calibrated, dynamic mathematical model, we compared the status quo diagnostic algorithm, emphasizing sputum smear, against an algorithm incorporating Xpert for initial diagnosis. Results were projected over 10- and 20-y time periods starting from 2012. Compared to status quo, implementation of Xpert would avert 132,000 (95% CI: 55,000–284,000) TB cases and 182,000 (97,000–302,000) TB deaths in southern Africa over the 10 y following introduction, and would reduce prevalence by 28% (14%–40%) by 2022, with more modest reductions in incidence. Health system costs are projected to increase substantially with Xpert, by US$460 million (294–699 million) over 10 y. Antiretroviral therapy for HIV represents a substantial fraction of these additional costs, because of improved survival in TB/HIV-infected populations through better TB case-finding and treatment. Costs for treating MDR-TB are also expected to rise significantly with Xpert scale-up. Relative to status quo, Xpert has an estimated cost-effectiveness of US$959 (633–1,485) per disability-adjusted life-year averted over 10 y. Across countries, cost-effectiveness ratios ranged from US$792 (482–1,785) in Swaziland to US$1,257 (767–2,276) in Botswana. Assessing outcomes over a 10-y period focuses on the near-term consequences of Xpert adoption, but the cost-effectiveness results are conservative, with cost-effectiveness ratios assessed over a 20-y time horizon approximately 20% lower than the 10-y values.Conclusions
Introduction of Xpert could substantially change TB morbidity and mortality through improved case-finding and treatment, with more limited impact on long-term transmission dynamics. Despite extant uncertainty about TB natural history and intervention impact in southern Africa, adoption of Xpert evidently offers reasonable value for its cost, based on conventional benchmarks for cost-effectiveness. However, the additional financial burden would be substantial, including significant increases in costs for treating HIV and MDR-TB. Given the fundamental influence of HIV on TB dynamics and intervention costs, care should be taken when interpreting the results of this analysis outside of settings with high HIV prevalence. Please see later in the article for the Editors'' Summary 相似文献13.
Lukas Fenner Marie Ballif Claire Graber Venerandah Nhandu Jean Claude Dusingize Claudia P. Cortes Gabriela Carriquiry Kathryn Anastos Daniela Garone Eefje Jong Joachim Charles Gnokoro Omar Sued Samuel Ajayi Lameck Diero Kara Wools-Kaloustian Sasisopin Kiertiburanakul Barbara Castelnuovo Charlotte Lewden Nicolas Durier Timothy R. Sterling Matthias Egger for the International epidemiological Databases to Evaluate AIDS 《PloS one》2013,8(10)
Objectives
In resource-constrained settings, tuberculosis (TB) is a common opportunistic infection and cause of death in HIV-infected persons. TB may be present at the start of antiretroviral therapy (ART), but it is often under-diagnosed. We describe approaches to TB diagnosis and screening of TB in ART programs in low- and middle-income countries.Methods and findings
We surveyed ART programs treating HIV-infected adults in sub-Saharan Africa, Asia and Latin America in 2012 using online questionnaires to collect program-level and patient-level data. Forty-seven sites from 26 countries participated. Patient-level data were collected on 987 adult TB patients from 40 sites (median age 34.7 years; 54% female). Sputum smear microscopy and chest radiograph were available in 47 (100%) sites, TB culture in 44 (94%), and Xpert MTB/RIF in 23 (49%). Xpert MTB/RIF was rarely available in Central Africa and South America. In sites with access to these diagnostics, microscopy was used in 745 (76%) patients diagnosed with TB, culture in 220 (24%), and chest X-ray in 688 (70%) patients. When free of charge culture was done in 27% of patients, compared to 21% when there was a fee (p = 0.033). Corresponding percentages for Xpert MTB/RIF were 26% and 15% of patients (p = 0.001). Screening practices for active disease before starting ART included symptom screening (46 sites, 98%), chest X-ray (38, 81%), sputum microscopy (37, 79%), culture (16, 34%), and Xpert MTB/RIF (5, 11%).Conclusions
Mycobacterial culture was infrequently used despite its availability at most sites, while Xpert MTB/RIF was not generally available. Use of available diagnostics was higher when offered free of charge. 相似文献14.
Gabriela Carriquiry Larissa Otero Elsa Gonz��lez-Lagos Carlos Zamudio Eduardo S��nchez Pamela Nabeta Miguel Campos Juan Echevarr��a Carlos Seas Eduardo Gotuzzo 《PloS one》2012,7(9)
Background
Diagnosis of pulmonary tuberculosis (TB) among human immunodeficiency virus (HIV) patients remains complex and demands easy to perform and accurate tests. Xpert®MTB/RIF (MTB/RIF) is a molecular TB diagnostic test which is rapid and convenient; the test requires minimal human resources and reports results within two hours. The majority of performance studies of MTB/RIF have been performed in high HIV burden settings, thus TB diagnostic studies among HIV patients in low HIV prevalence settings such as Peru are still needed.Methodology/Principal Findings
From April 2010 to May 2011, HIV-positive patients with high clinical suspicion of TB were enrolled from two tertiary hospitals in Lima, Peru. Detection of TB by MTB/RIF was compared to a composite reference standard Löwenstein-Jensen (LJ) and liquid culture. Detection of rifampicin resistance was compared to the LJ proportion method. We included 131 patients, the median CD4 cell count was 154.5 cells/mm3 and 45 (34.4%) had TB. For TB detection among HIV patients, sensitivity of MTB/RIF was 97.8% (95% CI 88.4–99.6) (44/45); specificity was 97.7% (95% CI 91.9–99.4) (84/86); the positive predictive value was 95.7% (95% CI 85.5–98.8) (44/46); and the negative predictive value, 98.8% (95% CI 93.6–99.8) (84/85). MTB/RIF detected 13/14 smear-negative TB cases, outperforming smear microscopy [97.8% (44/45) vs. 68.9% (31/45); p = 0.0002]. For rifampicin resistance detection, sensitivity of MTB/RIF was 100% (95% CI 61.0–100.0) (6/6); specificity was 91.0% (95% CI 76.4–96.9) (30/33); the positive predictive value was 66.7% (95% CI 35.4–87.9) (6/9); and the negative predictive value was 100% (95% CI 88.7 –100.0) (30/30).Conclusions/Significance
In HIV patients in our population with a high clinical suspicion of TB, MTB/RIF performed well for TB diagnosis and outperformed smear microscopy. 相似文献15.
Padmapriya P. Banada Uvistra Naidoo Srinidhi Deshpande Farina Karim JoAnne L. Flynn Melanie O’Malley Martin Jones Oliver Nanassy Prakash Jeena David Alland 《PloS one》2016,11(3)
Background
Tuberculosis (TB) is difficult to diagnose in children using molecular tests, because children have difficulty providing respiratory samples. Stool could replace sputum for diagnostic TB testing if adequate sample processing techniques were available.Methods
We developed a rapid method to process large volumes of stool for downstream testing by the Xpert MTB/RIF (Xpert) TB-detection assay. The method was tested and optimized on stool samples spiked with known numbers of M. tuberculosis colony forming units (CFU), and stools from M. tuberculosis-infected cynomolgus macaques (Macaca fascicularis). Performance was scored on number of positive Xpert tests, the cycle thresholds (Cts) of the Xpert sample-processing control (SPC), and the Cts of the M. tuberculosis-specific rpoB probes. The method was then validated on 20 confirmed TB cases and 20 controls in Durban, South Africa.Results
The assay’s analytical limit of detection was 1,000 CFU/g of stool. As much as one gram of spiked stool could be tested without showing increased PCR inhibition. In analytical spiking experiments using human stool, 1g samples provided the best sensitivity compared to smaller amounts of sample. However, in Macaques with TB, 0.6g stool samples performed better than either 0.2g or 1.2g samples. Testing the stool of pediatric TB suspects and controls suggested an assay sensitivity of 85% (95% CI 0.6–0.9) and 84% (95% CI 0.6–0.96) for 0.6g and 1.2g stool samples, respectively, and a specificity of 100% (95% CI 0.77–1) and 94% (95% CI 0.7–0.99), respectively.Conclusion
This novel approach may permit simple and rapid detection of TB using pediatric stool samples. 相似文献16.
Sreenivas Achuthan Nair Neeraj Raizada Kuldeep Singh Sachdeva Claudia Denkinger Samuel Schumacher Puneet Dewan Shubhangi Kulsange Catharina Boehme Chinnambedu Nainarappan Paramsivan Nimalan Arinaminpathy 《PloS one》2016,11(2)
Background
Tuberculosis remains a major public health challenge for India. Various studies have documented different levels of TB and multi-drug resistant (MDR) TB among diverse groups of the population. In view of renewed targets set under the End TB strategy by 2035, there is an urgent need for TB diagnosis to be strengthened. Drawing on data from a recent, multisite study, we address key questions for TB diagnosis amongst symptomatics presenting for care: are there subgroups of patients that are more likely than others, to be positive for TB? In turn, amongst these positive cases, are there factors—apart from treatment history—that may be predictive for multi-drug resistance?Methods
We used data from a multi-centric prospective demonstration study, conducted from March 2012 to December 2013 in 18 sub-district level TB programme units (TUs) in India and covering a population of 8.8 million. In place of standard diagnostic tests, upfront Xpert MTB/RIF testing was offered to all presumptive TB symptomatics. Here, using data from this study, we used logistic regression to identify association between risk factors and TB and Rifampicin-Resistant TB among symptomatics enrolled in the study.Results
We find that male gender; history of TB treatment; and adult age compared with either children or the elderly are risk factors associated with high TB detection amongst symptomatics, across the TUs. While treatment history is found be a significant risk factor for rifampicin-resistant TB, elderly (65+ yrs) people have significantly lower risk than other age groups. However, pediatric TB cases have no less risk of rifampicin resistance as compared with adults (OR 1.23 (95% C.I. 0.85–1.76)). Similarly, risk of rifampicin resistance among both the genders was the same. These patterns applied across the study sites involved. Notably in Mumbai, amongst those patients with microbiological confirmation of TB, female patients showed a higher risk of having MDR-TB than male patients.Conclusion
Our results cast fresh light on the characteristics of symptomatics presenting for care who are most likely to be microbiologically positive for TB, and for rifampicin resistance. The challenges posed by TB control are complex and multifactorial: evidence from diverse sources, including retrospective studies such as that addressed here, can be invaluable in informing future strategies to accelerate declines in TB burden. 相似文献17.
Sarder Tanzir Hossain Petros Isaakidis Karuna D. Sagili Shayla Islam Md Akramul Islam Hemant Deepak Shewade S. M. Mostofa Kamal Ashaque Husain 《PloS one》2015,10(6)
Objectives
To determine, in areas supported by BRAC, Bangladesh i) the pre-diagnosis and pre-treatment attrition among presumptive and confirmed Multi-Drug Resistant Tuberculosis (MDR-TB) patients and ii) factors associated with attrition.Methods
This was a retrospective cohort study involving record review. Presumptive MDR-TB patients from peripheral microscopy centres serving 60% of the total population of Bangladesh were included in the study. Attrition and turnaround time for MDR-TB diagnosis by Xpert MTB/RIF and treatment initiation were calculated between July 2012 and June 2014.Results
Of 836 presumptive MDR-TB patients referred from 398 peripheral microscopy centres, 161 MDR-TB patients were diagnosed. The number of diagnosed MDR-TB patients was less than country estimates of MDR-TB patients (2000 cases) during the study period. Among those referred, pre-diagnosis and pre-treatment attrition was 17% and 21% respectively. Median turnaround time for MDR-TB testing, result receipt and treatment initiation was four, zero and five days respectively. Farmers (RR=2.3, p=0.01) and daily wage laborers (RR=2.1, p=0.04) had twice the risk of having pre-diagnosis attrition. Poor record-keeping and unreliable upkeep of presumptive MDR-TB patient databases were identified as challenges at the peripheral microscopy centres.Conclusion
There was a low proportion of pre-diagnosis and pre-treatment attrition in patients with presumptive and confirmed MDR-TB under programmatic conditions. However, the recording and reporting system did not detect all presumptive MDR-TB patients, highlighting the need to improve the system in order to prevent morbidity, mortality and transmission of MDR-TB in the community. 相似文献18.
Pren Naidoo Elizabeth du Toit Rory Dunbar Carl Lombard Judy Caldwell Anne Detjen S. Bertel Squire Donald A. Enarson Nulda Beyers 《PloS one》2014,9(7)
Background
Xpert MTB/RIF was introduced as a screening test for all presumptive tuberculosis cases in primary health services in Cape Town, South Africa.Study Aim
To compare multidrug-resistant tuberculosis (MDR-TB) treatment commencement times in MDRTBPlus Line Probe Assay and Xpert MTB/RIF-based algorithms in a routine operational setting.Methods
The study was undertaken in 10 of 29 high tuberculosis burden primary health facilities, selected through stratified random sampling. An observational study was undertaken as facilities transitioned to the Xpert MTB/RIF-based algorithm. MDR-TB diagnostic data were collected from electronic laboratory records and treatment data from clinical records and registers. Kaplan Meier time-to-event analysis was used to compare treatment commencement time, laboratory turnaround time and action delay between algorithms. A facility-level paired analysis was done: the median time-to-event was estimated per facility in each algorithm and mean differences between algorithms compared using a paired t-test. Cox proportional hazards regression was used to assess the effect of patient-level variables on treatment commencement time. The difference between algorithms was compared using the hazard ratio.Results
The median treatment commencement time in the Xpert MTB/RIF-based algorithm was 17 days (95% CI 13 to 22 days), with a median laboratory turnaround time (to result available in the laboratory) of <1 day (95% CI<1 to 1 day). There was a decrease of 25 days (95% CI 17 to 32 days, p<0.001) in median MDR-TB treatment commencement time in the Xpert MTB/RIF-based algorithm. We found no significant effect on treatment commencement times for the patient-level variables assessed.Conclusion
MDR-TB treatment commencement time was significantly reduced in the Xpert MTB/RIF-based algorithm. Changes in the health system may have contributed. However, an unacceptable level of delay remains. Health system and patient factors contributing to delay need to be evaluated and addressed to optimise test benefits. 相似文献19.
Irfan Ullah Arshad Javaid Zarfishan Tahir Obaid Ullah Aamer Ali Shah Fariha Hasan Najma Ayub 《PloS one》2016,11(1)
Background
Drug resistant tuberculosis (DR-TB) is a major public health problem in developing countries such as Pakistan.Objective
The current study was conducted to assess the frequency of drug resistant tuberculosis including multi drug resistance (MDR- TB) as well as risk factors for development of DR-TB, in Punjab, Pakistan.Methodology
Drug susceptibility testing (DST) was performed, using proportion method, for 2367 culture positive Mycobacterium tuberculosis (MTB) cases that were enrolled from January 2012 to December 2013 in the province of Punjab, Pakistan, against first-line anti-tuberculosis drugs. The data was analyzed using statistical software; SPSS version 18.Results
Out of 2367 isolates, 273 (11.5%) were resistant to at least one anti-TB drug, while 221 (9.3%) showed MDR- TB. Risk factors for development of MDR-TB were early age (ranges between 10–25 years) and previously treated TB patients.Conclusion
DR-TB is a considerable problem in Pakistan. Major risk factors are previous history of TB treatment and younger age group. It emphasizes the need for effective TB control Program in the country. 相似文献20.