Implementation Of Xpert Research Articles

Evaluation of GeneXpert MTB/Rif Ultra assay performance on formalin-fixed paraffin-embedded tissues for Mycobacterium tuberculosis detection.

We evaluated the Xpert MTB/Rif Ultra assay performance for Mycobacterium tuberculosis (MTB) detection in formalin-fixed paraffin-embedded tissue (FFPET) compared to mycobacterial culture or laboratory-developed MTB PCR test (LDT). FFPET samples with histological features suggestive of tuberculosis from 2018 to 2023 were selected. Five hundred microlitres of tissue lysis buffer was added to FFPET scrolls and incubated at 75 °C for 5 min. After adding 50 µl of proteinase K and overnight incubation at 56 °C, sample aliquots were processed as per the manufacturer's instructions. MTB culture or LDT assay results were used as a reference for sensitivity and specificity calculations. Of 51 eligible FFPET, 32 were positive for MTB either by culture or LDT PCR on FFPET. Xpert MTB/Rif Ultra detected MTB in 23/32 positive specimens [71.9%, 95% confidence interval (CI) 54.6-84.4%]. Of nine discordant specimens, seven were MTB positive by culture and two were identified by LDT MTB PCR only, as no specimen was submitted for MTB culture. Of 19 negative samples, 100% specificity (95% CI 83.2-100.0%) was attained via Xpert MTB/Rif Ultra. Implementation of Xpert MTB/Rif Ultra on FFPET within clinical laboratories is promising, given its improved turnaround time compared to MTB culture and ability to detect MTB in cases where no tissue is available for culture.

Implementation of GeneXpert for TB Testing in Low- and Middle-Income Countries: A Systematic Review

Current evidence indicates that the impact of GeneXpert for diagnosing TB in low- and middle-income countries (LMICs) has not demonstrated equivalent outcomes when compared to Xpert evaluations in upper-middle-income countries. Challenges associated with implementation are possible contributing factors preventing this innovative diagnostic technology from achieving more significant public health outcomes. This review aimed to assess the use of implementation science frameworks when reporting the enablers and barriers for the implementation of GeneXpert for diagnosing TB in LMICs. We conducted a qualitative systematic review of the peer-reviewed literature using PubMed, Medline, and Scopus. Eligible articles were those published between January 2010 and March 2020 that identified enablers and barriers to GeneXpert implementation, as well as the implementation approach delivered in an LMIC. Eleven studies were included in the review. Implementation barriers were found to be relatively consistent across studies and included patient-level factors, human resources, material resources, service implementation, service coordination, and technical operations. Few studies (n=5) identified enabling factors in the implementation of Xpert for TB testing. Identified enablers included strategies such as active case finding, expanding diagnostic algorithms, and daily transport of samples. The public health impact of Xpert TB testing interventions was commonly influenced by implementation barriers (n=4). Of the 11 studies, only 3 reported against an implementation framework. This review identified a commonality in implementation barriers and enablers that influenced the overall public health impact of GeneXpert. With greater transparency of these barriers and enablers, program planners can promote a more collaborative approach and adapt interventions. It is recommended that program planners use implementation science frameworks when conducting research and publishing. This will build an evidence base focused on implementation and thereby support programs to address implementation barriers and include enabling factors in program design.

Improving tuberculosis management in prisons: Impact of a rapid molecular point-of-care test

To improve tuberculosis (TB) diagnosis in prison, we evaluate the value of the XpertⓇMTB/RIF Ultra assay (Xpert) as point-of-care (POC) in a French prison hospital. We first validated Xpert use on raw sputum at the referent laboratory. Secondly, trained physicians at the prison hospital performed Xpert tests for each patient presenting TB symptoms. The results were compared with Xpert, microscopic examination, culture and drug susceptibility testing on the corresponding decontaminated specimens. 76 inmates were included in 15 months and 21 were diagnosed with TB. The overall sensitivity, specificity, positive and negative predictive values of Xpert were respectively: 92.3%, 100%, 100% and 98.7% on raw sputum. The efficiency of the molecular POC was confirmed by a concordance of 97% between Xpert findings from the prison hospital and culture results. Delay of microbiological diagnosis was reduced by about 18 days for 13 inmates with smear-negative sputum that avoid the mobilization of major means (escort, transport) to perform fibroscopic samples. Repeated Xpert negative results helped to speed the lifting of inmate isolation. The implementation of Xpert in prison could optimize the management of incarcerated patients and thus limit the spread of TB among inmates, carers and other staff.

Performance of Xpert/MTB/RIF assay for childhood pulmonary tuberculosis among HIV negative children with real world evidence in China

BackgroundRapid and accurate notification of childhood pulmonary tuberculosis (PTB) is a worldwide challenge. Although the Xpert MTB/RIF assay (Xpert) has been endorsed as the initial test for suspected PTB in many countries, limited studies have reported the performance of Xpert in childhood PTB. The aim of this study is to evaluate the real-world performance of Xpert for the detection of childhood PTB among HIV negative children in China. MethodsWe consecutively extracted the data of all patients ≤14 years with pulmonary disease through the electronic medical record (EMR) systems of Shanghai Public Health Clinical Center from January 2014 to December 2017. The clinical profile, the decision-making tests including AFB smear, solid/liquid culture, pathological examination and Xpert result were matched and assessed. The real diagnostic accuracy and the all-factors case notification rate for childhood PTB with the implementation of Xpert were evaluated. Results519 HIV negative cases ≤14 years with pulmonary disease were extracted from the data base. Of these, 145 had matched results, there were 374 non-matched cases including 346 with incomplete or unavailable data and 28 with NTM, BCG or an unidentified strain. For matched data, the overall sensitivity and specificity of the Xpert assay were 66.7% (32/48, 95%CI 0.52–0.80) and 87.6% (85/97, 95%CI 0.87–0.98) respectively against the gold standard; 34.6% (44/127, 95%CI 26.6–43.7) and 100% against the composite clinical reference standard (CCRS). The all-factors case notification rate by Xpert was 29%. ConclusionXpert/MTB RIF assay has acceptable sensitivity and excellent specificity for rapid diagnosis of children with pulmonary TB as well as for the detection of RIF resistance in China. However, implementation of Xpert for the initial diagnosis of childhood PTB is inadequate to meet the urgent requirement for rapid and accurate detection of childhood PTB.

Use of Xpert Contributes to Accurate Diagnosis, Timely Initiation, and Rational Use of Anti-TB Treatment Among Childhood Tuberculosis Cases in South Central Ethiopia.

BackgroundChildhood tuberculosis (TB) was under-prioritized, and only 15% of childhood TB cases are microbiologically confirmed. Hence, most childhood TB diagnoses are made on a clinical basis and prone to over- or under-treatment. Xpert is a rapid method for the diagnosis of childhood TB with high sensitivity.ObjectiveTo assess the use of Xpert for accurate diagnosis, timely initiation, and rational use of anti-TB treatment among childhood TB.MethodsIn 2016, the hospital facilitated the installation of the Xpert machine. We reviewed data trends over four consecutive years; two years before the arrival of the machine and two years following the implementation of Xpert. Data were extracted retrospectively from electronically stored databases and medical records and entered to SPSS 21 for analysis.ResultsIn the pre-intervention period (2014–2015), 404 cases of children presenting with symptoms or signs suggestive of TB (“presumptive TB”) were evaluated using AFB microscopy. A total of 254 (62.8%) TB diagnoses were made, of which 54 (21.3%) were confirmed by smear AFB while 200 (78.7%) were treated as smear-negative TB cases. The mean waiting time to start anti-TB treatment was 6.95 days [95% CI (3.71–10.90)]. During the intervention period (2016–2017), 371 children with presumptive TB were evaluated using Xpert. A total of 199 (53.6%) childhood TB cases were notified, of which 88 (44.2%) were Xpert positive and 111 (55.8%) were treated as Xpert-negative probable TB cases. The tendency to initiate anti-TB treatment for unconfirmed TB cases was reduced by a third. Compared with smear AFB, Xpert improved accuracy of diagnosing pediatric TB cases two-fold. The average waiting time to start anti-TB treatment was 1.33 days [95% CI (0.95–1.71)]. There was a significant reduction in the waiting time to start anti-TB treatment, with a mean time difference before and during intervention of 5.62 days [95% CI (1.68–9.56)].ConclusionXpert use was associated with a significant increase in the accuracy of identifying confirmed TB cases, reduced unnecessary anti-TB prescription, and shortened the time taken to start TB treatment.

Difficulties with the implemented xpert MTB/RIF for determining diagnosis of pulmonary and extrapulmonary tuberculosis in adults and children

Background and aimsHandling of PTB and EPTB patients with adequate standard detection of MTBC and anti-TB drug sensitivity using accurate and rapid methods could provide good TB management and clinical treatment outcomes. The Xpert MTB/RIF assay is an automated, cartridge-based NAAT that can simultaneously detect MTBC and RIF resistance within 2 h. The aim of this study was to evaluate the implementation of Xpert for determining diagnosis of PTB and EPTB in adults and children. MethodsA descriptive study was performed using e-TB Manager data from the MDR-TB Clinic at Dr. Soetomo Academic Hospital. Suspected TB cases were from the areas of East Java Province from January 2016 to December 2018. Xpert assay was conducted using standardized criteria for clinically suspected TB, and MTBC-positive results with RR were examined by the culture method using MGIT 960 BACTEC System. ResultsA total of 1181 (1181/3009, 39.25%) sputum samples from suspected new MDR-PTB cases tested positive for MTBC with 3.02% RR. Among 3893 sputum samples from previously treated probable MDR-PTB cases tested using Xpert, 1936 (49.73%) were MTBC positive with 13.20% RR. Among 59 new suspected MDR-PTB cases tested using MGIT 960 BACTEC System, 55 tested positive for MTBC, although all RR strains were highly sensitive to amikacin (100%), kanamycin (95%), and ofloxacin (89%). A total of 49 children with suspected PTB were tested using Xpert, revealing low positivity (12%) for MTBC, with all RR strains being rifampicin sensitive (RS). Of the 86 suspected EPTB cases tested using Xpert, very few were MTBC-positive (26%), with 91% RS. ConclusionsThis study revealed that in adults and children with PTB and EPTB, the Xpert assay achieved a low positivity detection rate for MTBC in samples from new or previously treated cases, and this could be the result of many factors.

Xpert negative means no TB: A mixed-methods study into early implementation of Xpert in Puducherry, India.

Introduction:Xpert MTB/RIF was implemented in 2016 as the initial diagnostic test for extrapulmonary, pediatric, and human immunodeficiency virus–associated tuberculosis (TB) and as an add-on test for sputum microscopy–negative patients under Revised National TB Control Programme, Puducherry, India. We intended to study the change in TB case notification rates (CNRs) after 2015 and explore the enablers and barriers for implementation of Xpert.Materials and Methods:Sequential mixed-methods study, quantitative phase followed by a descriptive qualitative phase (key informant interviews with healthcare providers in the program).Results:The TB (all forms) CNR increased in 2016 followed by a drop to 2015 levels in 2017. There was a reduction in patients notified as sputum-negative pulmonary TB and pediatric TB during 2016–2017. Healthcare providers used a negative Xpert result in ruling out TB among patients who would previously get diagnosed clinically. Perceived benefits of Xpert were efficiency, rapid results, and detecting resistance. Barriers included poor awareness among medical colleges and the private sector, difficulty in motivating sputum microscopy–negative patients for Xpert, and incompletely filled referral forms.Conclusion:Xpert-negative results should be interpreted cautiously after clinical assessment. Identified barriers should be addressed to ensure that all eligible undergo testing.

Pre-treatment loss to follow-up among patients with rifampicin-resistant tuberculosis in Baluchistan, Pakistan, 2012-17: a retrospective cohort study

Background: Patients with rifampicin-resistant TB (RR-TB) pretreatment loss to follow-up continue to be a global health challenge. Although the accuracy of diagnosis significantly increased with the implementation of Xpert MTB/RIF assay, which is a rapid molecular based test and more sensitive than conventional microscopy which detects MTB even present in small limit of 136 MTB/ml of sputum, but still data suggest a wide treatment initiation gap among diagnosed. This study was done to assess the proportion of patients with RR-TB pretreatment lost to follow-up and the socio-demographic factors associated with this in Balochistan, Pakistan. Methods: This was a retrospective cohort study based on review of the routinely managed program records. The data included all patients with RR-TB detected at Fatima Jinnah Chest & General Hospital Quetta and District Head Quarter Hospital Loralai, Xpert sites and enrolled at programmatic management of drug resistant TB (PMDT) sites during 2012-2017. Data collected was double-entered, validated and analyzed using EpiData. Results: Of the 396 patients with RR-TB detected during 2012-17, 78 (19.8%) underwent pre-treatment lost to follow-up. The mean age of those detected with RR-TB was 37 years (SD ±16.98); 189 (48%) were of age group 15-34, while 60% were female. Among 84 individuals referred out to other facilities, only 6 started treatment. Almost half of the ‘pretreatment lost to follow-up’ patients were from age group 15-34, while 43 were from within the Quetta and Loralai districts. Conclusions: The high proportion of patients with RR-TB that were pre-treatment lost to follow-up in Balochistan needs immediate strategies to establish linkages between Xpert and PMDT sites for the timely management of patients to prevent the spread of RR-TB infection.

Impact of Xpert MTB/RIF and decentralized care on linkage to care and drug-resistant tuberculosis treatment outcomes in Johannesburg, South Africa

BackgroundIn 2011, South Africa improved its ability to test for rifampicin-resistant TB (RR-TB) by introducing GeneXpert MTB/RIF. At the same time, the South African National TB program adopted a policy decentralized, outpatient treatment for drug resistant (DR-) TB. We aim to analyze the impact of these changes on linkage to care and DR-TB treatment outcomes.MethodsWe retrospectively matched adult patients diagnosed with laboratory-confirmed RR-TB in Johannesburg from 07/2011–06/2012 (early cohort) and 07/2013–06/2014 (late cohort) with records of patients initiating DR-TB treatment at one of the city’s four public sector treatment sites. We determine the proportion of persons diagnosed with RR-TB who initiated DR-TB treatment and report time to treatment initiation (TTI) before and after the implementation of Xpert MTB/RIF roll-out in Johannesburg, South Africa. We conducted a sub-analysis among those who initiated DR-TB treatment at the decentralized outpatient DR-TB centers to determine if delays in treatment initiation have a subsequent impact on treatment outcomes.ResultsFive hundred ninety four patients were enrolled in the early cohort versus 713 in the late cohort. 53.8 and 36.8% of patients were diagnosed with multi-drug resistant TB in the early and late cohorts, respectively. The proportion of RR-TB confirmed cases diagnosed by Xpert MTB/RIF increased from 43.4 to 60.5% between the early and late cohorts, respectively. The proportion who initiated treatment increased from 43.1% (n = 256) to 60.3% (n = 430) in the late cohort. Pre-treatment mortality during the early and the late cohort reduced significantly from 17.5 to 5.8% while lost to follow-up remained high.Although TTI reduced by a median of 19 days, from 33 days (IQR 12–52) in the early cohort to 14 days (IQR 7–31) in the late cohort, this did not translate to improved treatment outcomes and we found no difference in terms of treatment success or on-treatment mortality for those that initiated without delay vs. those that deferred initiation.ConclusionPre-treatment mortality reduced significantly during late Xpert MTB/RIF coverage but there was no significant difference after treatment was initiated. Despite improvements there is still a significant diagnosis and treatment gap for patients diagnosed with RR-TB and improving treatment outcomes remains critical.

The implementation of Xpert MTB/RIF assay for diagnosis of tuberculosis in Nepal: A mixed-methods analysis.

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.

The impact of implementing a Xpert MTB/RIF algorithm on drug-sensitive pulmonary tuberculosis: a retrospective analysis.

Xpert MTB/RIF (Xpert) is the preferred first-line test for all persons with tuberculosis (TB) symptoms in South Africa in line with a diagnostic algorithm. This study evaluates pre- and post-implementation trends in diagnostic practices for drug-sensitive, pulmonary TB in adults in an operational setting, following the introduction of the Xpert-based algorithm. We retrospectively analysed data from the national TB database for Greater Tzaneen sub-district, Limpopo Province. Trends in a number of cases, diagnosis and outcome and characteristics associated with death are reported. A total of 8407 cases were treated from 2008 until 2015, with annual cases registered decreasing by 31·7% over that time period (from 1251 to 855 per year). After implementation of Xpert, 69·9% of cases were diagnosed by Xpert, 29·4% clinically, 0·6% by smear microscopy and 0·1% by culture. Cases with a recorded microbiological test increased from 76·2% to 96·4%. Cases started on treatment without confirmation, but with a negative microbiological test increased from 7·1% to 25·7%. Case fatality decreased from 15·0% to 9·8%, remaining consistently higher in empirically treated groups, regardless of HIV status. Implementation of the algorithm coincided with a reduced number of TB cases treated and improved coverage of microbiological testing; however, a substantial proportion of cases continued to start treatment empirically.

Implementation of Xpert MTB/RIF in 22 high tuberculosis burden countries: are we making progress?

Uptake of Xpert in 22 high burden countries has progressed well since 2014, although more can be done to reach scale http://ow.ly/Whvu30dpqVI

Implementation of the Xpert MTB/RIF assay for tuberculosis in Mongolia: a qualitative exploration of barriers and enablers.

ObjectiveThe aim of our study was to identify barriers and enablers to implementation of the Xpert MTB/RIF test within Mongolia’s National Tuberculosis Program.MethodsTwenty-foursemi-structured interviews were conducted between June and September 2015 with laboratory staff and tuberculosis physicians in Mongolia’s capital Ulaanbaatar and regional towns where Xpert MTB/RIF testing had been implemented. Interviews were recorded, transcribed, translated and analysed thematically using NVIVO qualitative analysis software.ResultsEight laboratory staff (five from the National Tuberculosis Reference Laboratory in Ulaanbaatar and three from provincial laboratories) and sixteen tuberculosis physicians (five from the Mongolian National Center for Communicable Diseases in Ulaanbaatar, four from district tuberculosis clinics in Ulaanbaatar and seven from provincial tuberculosis clinics) were interviewed. Major barriers to Xpert MTB/RIF implementation identified were: lack of awareness of program guidelines; inadequate staffing arrangements; problems with cartridge supply management; lack of local repair options for the Xpert machines; lack of regular formal training; paper based system; delayed treatment initiation due to consensus meeting and poor sample quality. Enablers to Xpert MTB/RIF implementation included availability of guidelines in the local language; provision of extra laboratory staff, shift working arrangements and additional modules; capacity for troubleshooting internally; access to experts; opportunities for peer learning; common understanding of diagnostic algorithms and decentralised testing.ConclusionOur study identified a number of barriers and enablers to implementation of Xpert MTB/RIF in the Mongolian National Tuberculosis Program. Lessons learned from this study can help to facilitate implementation of Xpert MTB/RIF in other Mongolian locations as well as other low-and middle-income countries.

Results of Xpert® MTB/RIF implementation in Kyrgyzstan.

In July 2012, the United States Agency for International Development (USAID) Quality Health Care Project introduced the Xpert® MTB/RIF assay at the facility level of the primary health care system in Kyrgyzstan. This study analysed the results of the implementation of Xpert. Test results from 2734 patients from July 2012 to December 2014 were analysed. The sensitivity and specificity of Xpert in routine programme conditions were evaluated using culture and phenotypic drug susceptibility testing (DST) as gold standard. Contribution to early start of treatment for multidrug-resistant tuberculosis (MDR-TB) was expressed as the median time between availability of the test result and start of treatment. Compared to culture, the sensitivity and specificity of Xpert were respectively 92.7% and 90.4%. For the detection of rifampicin (RMP) resistance, Xpert sensitivity and specificity were respectively 90.1% and 90.7%. The median time to initiation of MDR-TB treatment decreased to 10 days (interquartile range [IQR] 6-16) in 2014 from 20 days (IQR 12-40, P < 0.001) in 2013. The Xpert assay demonstrated good agreement in the detection of both Mycobacterium tuberculosis and RMP-resistant pulmonary TB in routine clinical practice. Although Xpert improved the time to treatment initiation from 2013 to 2014, more efforts are needed to further reduce this delay.

Delays and loss to follow-up before treatment of drug-resistant tuberculosis following implementation of Xpert MTB/RIF in South Africa: A retrospective cohort study.

BackgroundSouth Africa has a large burden of rifampicin-resistant tuberculosis (RR-TB), with 18,734 patients diagnosed in 2014. The number of diagnosed patients has increased substantially with the introduction of the Xpert MTB/RIF test, used for tuberculosis (TB) diagnosis for all patients with presumptive TB. Routine aggregate data suggest a large treatment gap (pre-treatment loss to follow-up) between the numbers of patients with laboratory-confirmed RR-TB and those reported to have started second-line treatment. We aimed to assess the impact of Xpert MTB/RIF implementation on the delay to treatment initiation and loss to follow-up before second-line treatment for RR-TB across South Africa.Methods and findingsA nationwide retrospective cohort study was conducted to assess second-line treatment initiation and treatment delay among laboratory-diagnosed RR-TB patients. Cohorts, including approximately 300 sequentially diagnosed RR-TB patients per South African province, were drawn from the years 2011 and 2013, i.e., before and after Xpert implementation. Patients with prior laboratory RR-TB diagnoses within 6 mo and currently treated patients were excluded. Treatment initiation was determined through data linkage with national and local treatment registers, medical record review, interviews with health care staff, and direct contact with patients or household members. Additional laboratory data were used to track cases. National estimates of the percentage of patients who initiated treatment and time to treatment were weighted to account for the sampling design.There were 2,508 and 2,528 eligible patients in the 2011 and 2013 cohorts, respectively; 92% were newly diagnosed with RR-TB (no prior RR-TB diagnoses). Nationally, among the 2,340 and 2,311 new RR-TB patients in the 2011 and 2013 cohorts, 55% (95% CI 53%–57%) and 63% (95% CI 61%–65%), respectively, started treatment within 6 mo of laboratory receipt of their diagnostic specimen (p < 0.001). However, in 2013, there was no difference in the percentage of patients who initiated treatment at 6 mo between the 1,368 new RR-TB patients diagnosed by Xpert (62%, 95% CI 59%–65%) and the 943 diagnosed by other methods (64%, 95% CI 61%–67%) (p = 0.39). The median time to treatment decreased from 44 d (interquartile range [IQR] 20–69) in 2011 to 22 d (IQR 2–43) in 2013 (p < 0.001). In 2013, across the nine provinces, there were substantial variations in both treatment initiation (range 51%–73% by 6 mo) and median time to treatment (range 15–36 d, n = 1,450), and only 53% of the 1,448 new RR-TB patients who received treatment were recorded in the national RR-TB register.This retrospective study is limited by the lack of information to assess reasons for non-initiation of treatment, particularly pre-treatment mortality data. Other limitations include the use of names and dates of birth to locate patient-level data, potentially resulting in missed treatment initiation among some patients.ConclusionsIn 2013, there was a large treatment gap for RR-TB in South Africa that varied significantly across provinces. Xpert implementation, while reducing treatment delay, had not contributed substantially to reducing the treatment gap in 2013. However, given improved case detection with Xpert, a larger proportion of RR-TB patients overall have received treatment, with reduced delays. Nonetheless, strategies to further improve linkage to treatment for all diagnosed RR-TB patients are urgently required.

Low implementation of Xpert MTB/RIF among HIV/TB co-infected adults in the International epidemiologic Databases to Evaluate AIDS (IeDEA) program.

ObjectiveXpert MTB/RIF is recommended by the World Health Organization (WHO) as the initial tuberculosis (TB) diagnostic test in individuals suspected of HIV-associated TB. We sought to evaluate field implementation of Xpert among a cohort of HIV/TB co-infected individuals, including availability, utilization and outcomes.DesignObservational cohort study (patient-level data) and cross-sectional study (site-level Xpert availability data).MethodsData were collected at 30 participating International epidemiologic Databases to Evaluate AIDS (IeDEA) sites in 18 countries from January 2012-January 2016. All patients were HIV-infected and diagnosed with TB, either bacteriologically or clinically, and followed until a determination of TB treatment outcome. We used multivariable modified Poisson regression to estimate adjusted relative risk (RR) and 95% confidence intervals for unfavorable TB treatment outcomes.ResultsMost sites (63%) had access to Xpert, either in the clinic (13%), in the same facility (20%) or offsite (30%). Among 2722 HIV/TB patients included, median age was 35.4 years and 41% were female; BMI and CD4 count were low. Overall, most patients (76%) received at least one TB test; 45% were positive. Only 4% of all patients were tested using Xpert: 64% were Xpert-positive, 13% showed rifampicin (RIF) resistance and 30% were extrapulmonary (EPTB) or both pulmonary-EPTB. Treatment outcomes were mostly favorable (77%) and we found little association between Xpert use and an unfavorable TB treatment outcome (RR 1.25, 95%CI: 0.83, 1.90).ConclusionsIn this cohort, Xpert utilization was low even though the majority of sites had access to the test. Our findings show the need for expanded implementation and further research exploring barriers to use in low-resource settings.

Implementation of Xpert MTB/RIF in Uganda: Missed Opportunities to Improve Diagnosis of Tuberculosis.

Background. The effect of Xpert MTB/RIF (Xpert) scale-up on patient outcomes in low-income settings with a high tuberculosis (TB) burden has not been established. We sought to characterize the effectiveness of Xpert as implemented across different levels of the healthcare system in Uganda.Methods. We reviewed laboratory records from 2012 to 2014 at 18 health facilities throughout Uganda. In 8 facilities, Xpert had been implemented onsite since 2012, and in 10 sites Xpert was available as an offsite referral test from another facility. We describe Xpert testing volumes by facility, Xpert and smear microscopy results, and downtime due to malfunction and cartridge stockouts. We compare TB treatment initiation as well as time to treatment between facilities implementing Xpert and those that did not.Results. The median number of Xpert assays run at implementing facilities was 25/month (interquartile range [IQR], 10–63), amounting to 8% of total capacity. Among 1251 assays run for a new TB diagnosis, 19% were positive. Among 1899 patients with smear-negative presumptive TB, the proportion starting TB treatment was similar between Xpert facilities (11%; 95% confidence interval [CI], 9%–13%) and non-Xpert facilities (9%; 95% CI, 8%–11%; P = .325). In Xpert facilities, a positive Xpert preceded TB treatment initiation in only 12 of 70 (17%) smear-negative patients initiated on treatment.Conclusions. Xpert was underutilized in Uganda and did not significantly increase the number of patients starting treatment for TB. Greater attention must be paid to appropriate implementation of novel diagnostic tests for TB if these new tools are to impact patient important outcomes.

Immunochromatographic Assay for Detection of Mycobacterium Tuberculosis Complex in Clinical Isolates at Instituto de Infectologia Emilio Ribas, Brazil

Immunochromatographic Assay for Detection of Mycobacterium Tuberculosis Complex in Clinical Isolates at Instituto de Infectologia Emilio Ribas, Brazil Tuberculosis results in an estimated 1.5 million deaths each year and the worldwide number of new cases continues high. For decades, tuberculosis diagnosis in high-burden countries was almost completely based on sputum microscopy. Increasing rates of drug-resistance remains a severe threat that has drawn greater attention from worldwide tuberculosis control programs. We evaluated the performance of TB Ag MPT64 Test directly from 554 BACTEC MGIT 960 (or BACTEC FX, for blood and bone marrow) culture-positive samples: 391 were identified as M. tuberculosis complex and 95 as nontuberculosis mycobacteria. This immunochromatographic assay is easy, sensitive, and does not require a high level of skill or specific equipment. Since 2015, the implementation of Xpert MTB/RIF system is happening in Brazil supported by the Ministry of Health of Brazil, and this diagnostic technology provides a rapid diagnostic test for tuberculosis and rifampicin resistance.

Implementing the Xpert® MTB/RIF Diagnostic Test for Tuberculosis and Rifampicin Resistance: Outcomes and Lessons Learned in 18 Countries.

BackgroundThe 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.MethodsXpert 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.FindingsIn 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.ConclusionThe 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.

Impact of point-of-care implementation of Xpert® MTB/RIF: Product vs. process innovation

Impact of point-of-care implementation of Xpert® MTB/RIF: Product vs. process innovation