ArticlesFeasibility, accuracy, and clinical effect of point-of-care Xpert MTB/RIF testing for tuberculosis in primary-care settings in Africa: a multicentre, randomised, controlled trial
Introduction
A reversal in the incidence of tuberculosis is a key component of the UN Millennium Development Goals for 2015.1 Although substantial progress has been made worldwide,2 tuberculosis remains a major cause of morbidity and mortality in sub-Saharan Africa,3 and several high-burden countries are not on track to substantively reduce their burden of tuberculosis.4 Smear microscopy, which is often done in primary-care clinics in such settings, is frequently used for the diagnosis of tuberculosis, and it can rapidly affect treatment decisions. However, it misses 40–60% of cases, and does least well in people with advanced immunosuppression.5 Tests that are rapid, accurate, and deployable at the point of care are projected to substantially reduce tuberculosis-related morbidity and mortality,6, 7 although empirical evidence is in very short supply.
The Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA, USA) is a US Food and Drug Administration-approved, automated nucleic-acid amplification test that can detect both Mycobacterium tuberculosis (MTB) complex DNA and rifampicin (RIF) resistance within 2 h.8 In 2011, it was endorsed by WHO,9 and is being piloted or integrated into the national algorithms of a growing number of high-burden countries, where it will be based at subdistrict or district level.10
The accuracy of Xpert MTB/RIF is well validated: one test detects about 88% of culture-confirmed cases of pulmonary tuberculosis, correctly identifies about 98% of patients without tuberculosis, and can detect up to 67% of cases missed by smear microscopy.11 It can detect 94% of rifampicin-resistant tuberculosis cases and correctly classify 98% of rifampicin-susceptible cases.11 Preliminary data suggest Xpert MTB/RIF could accelerate and improve tuberculosis case detection,8, 12, 13, 14 and modelling studies project it to be cost effective15 and have a substantial effect on patient health in HIV-endemic regions.16
Despite the continuing roll out and piloting of Xpert MTB/RIF, no randomised empirical data exist to show whether its improved accuracy relative to smear microscopy improves patient-important outcomes and endpoints such as morbidity and mortality. Although small observational studies in South Africa13, 17, 18 have described the feasibility of Xpert MTB/RIF implementation at the point of care, whether their findings can be generalised to other countries is uncertain, as is whether point-of-care Xpert MTB/RIF improves same-day clinical decision making. The latter question is crucial because up to 40% of patients who test positive do not return for their results in tuberculosis-endemic settings.8, 19, 20 To better understand these important issues, which inform policy decisions relevant to the scale-up of Xpert MTB/RIF, we did a randomised controlled trial to examine the feasibility, accuracy, and clinical effect of Xpert MTB/RIF deployed at the point of care compared with smear microscopy in five primary-care health-care facilities in areas of southern Africa with a high HIV prevalence.
Section snippets
Study design and participants
We did a pragmatic, randomised, parallel-group, multicentre trial. After obtaining written informed consent, we consecutively enrolled patients aged 18 years or older who presented to periurban primary-care tuberculosis clinics with attached treatment facilities and microscopy laboratories in Cape Town (South Africa; here the microscopy laboratory was close by rather than attached to the facility), Durban (South Africa), Harare (Zimbabwe), Lusaka (Zambia), and Mbeya (Tanzania). We enrolled
Results
Between April 12, 2011, and March 30, 2012, we randomly assigned 758 patients to the smear microscopy group and 744 to the Xpert MTB/RIF group (figure 1), 182 and 185 of whom were culture positive, respectively (p=0·70). Six (2%) of the 345 culture-positive patients who were tested for multidrug resistance had multidrug-resistant tuberculosis. 439 (58%) of 758 patients in the smear microscopy group were infected with HIV compared with 456 (61%) of 744 in the Xpert MTB/RIF group (p=0·18).
Discussion
This multicentre study is the first randomised controlled trial of Xpert MTB/RIF, and the first to compare its feasibility at the point of care to that in the laboratory and the effect on clinically important outcomes (panel). Xpert MTB/RIF did not reduce overall tuberculosis-related morbidity (our primary outcome), but our results do show that Xpert MTB/RIF undertaken by a minimally trained nurse in a primary-care setting is feasible, and has similar sensitivity, better specificity, and
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2022, iScienceCitation Excerpt :Second-line therapies are available for treating such cases, which are given for more extended periods, ranging from 9 to 20 months depending upon the treatment regimen (Lange et al., 2019; WHO, 2019b; Migliori et al., 2017). In some cases, MDR TB is detected with GeneXpert, whereby one of the second-line therapies is started (Theron et al., 2014; Dorman et al., 2018; Di Tanna et al., 2019). However, in all other cases, where no clear information is available, treatment is typically started with Category-I and evaluated periodically and switched to different treatment categories if found necessary after 2 to 4 months of initiating therapy.
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