Journal Article > ResearchFull Text
Lancet. 2011 April 19; Volume 377 (Issue 9776); DOI:10.1016/S0140-6736(11)60438-8
Boehme CC, Nicol MP, Nabeta P, Michael JS, Gotuzzo E, et al.
Lancet. 2011 April 19; Volume 377 (Issue 9776); DOI:10.1016/S0140-6736(11)60438-8
BACKGROUND: The Xpert MTB/RIF test (Cepheid, Sunnyvale, CA, USA) can detect tuberculosis and its multidrug-resistant form with very high sensitivity and specificity in controlled studies, but no performance data exist from district and subdistrict health facilities in tuberculosis-endemic countries. We aimed to assess operational feasibility, accuracy, and effectiveness of implementation in such settings. METHODS: We assessed adults (≥18 years) with suspected tuberculosis or multidrug-resistant tuberculosis consecutively presenting with cough lasting at least 2 weeks to urban health centres in South Africa, Peru, and India, drug-resistance screening facilities in Azerbaijan and the Philippines, and an emergency room in Uganda. Patients were excluded from the main analyses if their second sputum sample was collected more than 1 week after the first sample, or if no valid reference standard or MTB/RIF test was available. We compared one-off direct MTB/RIF testing in nine microscopy laboratories adjacent to study sites with 2-3 sputum smears and 1-3 cultures, dependent on site, and drug-susceptibility testing. We assessed indicators of robustness including indeterminate rate and between-site performance, and compared time to detection, reporting, and treatment, and patient dropouts for the techniques used. FINDINGS: We enrolled 6648 participants between Aug 11, 2009, and June 26, 2010. One-off MTB/RIF testing detected 933 (90·3%) of 1033 culture-confirmed cases of tuberculosis, compared with 699 (67·1%) of 1041 for microscopy. MTB/RIF test sensitivity was 76·9% in smear-negative, culture-positive patients (296 of 385 samples), and 99·0% specific (2846 of 2876 non-tuberculosis samples). MTB/RIF test sensitivity for rifampicin resistance was 94·4% (236 of 250) and specificity was 98·3% (796 of 810). Unlike microscopy, MTB/RIF test sensitivity was not significantly lower in patients with HIV co-infection. Median time to detection of tuberculosis for the MTB/RIF test was 0 days (IQR 0-1), compared with 1 day (0-1) for microscopy, 30 days (23-43) for solid culture, and 16 days (13-21) for liquid culture. Median time to detection of resistance was 20 days (10-26) for line-probe assay and 106 days (30-124) for conventional drug-susceptibility testing. Use of the MTB/RIF test reduced median time to treatment for smear-negative tuberculosis from 56 days (39-81) to 5 days (2-8). The indeterminate rate of MTB/RIF testing was 2·4% (126 of 5321 samples) compared with 4·6% (441 of 9690) for cultures. INTERPRETATION: The MTB/RIF test can effectively be used in low-resource settings to simplify patients' access to early and accurate diagnosis, thereby potentially decreasing morbidity associated with diagnostic delay, dropout and mistreatment. FUNDING: Foundation for Innovative New Diagnostics, Bill & Melinda Gates Foundation, European and Developing Countries Clinical Trials Partnership (TA2007.40200.009), Wellcome Trust (085251/B/08/Z), and UK Department for International Development.
Journal Article > CommentaryFull Text
J Int AIDS Soc. 2020 January 1; Volume 23 (Issue 1); DOI:10.1002/jia2.25438
Gonzalez Fernandez L, Casas EDT, Singh SN, Churchyard GJ, Brigden G, et al.
J Int AIDS Soc. 2020 January 1; Volume 23 (Issue 1); DOI:10.1002/jia2.25438
INTRODUCTION:
Tuberculosis (TB) is a leading cause of mortality among people living with HIV (PLHIV). An invigorated global END TB Strategy seeks to increase efforts in scaling up TB preventive therapy (TPT) as a central intervention for HIV programmes in an effort to contribute to a 90% reduction in TB incidence and 95% reduction in mortality by 2035. TPT in PLHIV should be part of a comprehensive approach to reduce TB transmission, illness and death that also includes TB active case-finding and prompt, effective and timely initiation of anti-TB therapy among PLHIV. However, the use and implementation of preventive strategies has remained deplorably inadequate and today TB prevention among PLHIV has become an urgent priority globally.
DISCUSSION:
We present a summary of the current and novel TPT regimens, including current evidence of use with antiretroviral regimens (ART). We review challenges and opportunities to scale-up TB prevention within HIV programmes, including the use of differentiated care approaches and demand creation for effective TB/HIV services delivery. TB preventive vaccines and diagnostics, including optimal algorithms, while important topics, are outside of the focus of this commentary.
CONCLUSIONS:
A number of new tools and strategies to make TPT a standard of care in HIV programmes have become available. The new TPT regimens are safe and effective and can be used with current ART, with attention being paid to potential drug-drug interactions between rifamycins and some classes of antiretrovirals. More research and development is needed to optimize TPT for small children, pregnant women and drug-resistant TB (DR-TB). Effective programmatic scale-up can be supported through context-adapted demand creation strategies and the inclusion of TPT in client-centred services, such as differentiated service delivery (DSD) models. Robust collaboration between the HIV and TB programmes represents a unique opportunity to ensure that TB, a preventable and curable condition, is no longer the number one cause of death in PLHIV.
Tuberculosis (TB) is a leading cause of mortality among people living with HIV (PLHIV). An invigorated global END TB Strategy seeks to increase efforts in scaling up TB preventive therapy (TPT) as a central intervention for HIV programmes in an effort to contribute to a 90% reduction in TB incidence and 95% reduction in mortality by 2035. TPT in PLHIV should be part of a comprehensive approach to reduce TB transmission, illness and death that also includes TB active case-finding and prompt, effective and timely initiation of anti-TB therapy among PLHIV. However, the use and implementation of preventive strategies has remained deplorably inadequate and today TB prevention among PLHIV has become an urgent priority globally.
DISCUSSION:
We present a summary of the current and novel TPT regimens, including current evidence of use with antiretroviral regimens (ART). We review challenges and opportunities to scale-up TB prevention within HIV programmes, including the use of differentiated care approaches and demand creation for effective TB/HIV services delivery. TB preventive vaccines and diagnostics, including optimal algorithms, while important topics, are outside of the focus of this commentary.
CONCLUSIONS:
A number of new tools and strategies to make TPT a standard of care in HIV programmes have become available. The new TPT regimens are safe and effective and can be used with current ART, with attention being paid to potential drug-drug interactions between rifamycins and some classes of antiretrovirals. More research and development is needed to optimize TPT for small children, pregnant women and drug-resistant TB (DR-TB). Effective programmatic scale-up can be supported through context-adapted demand creation strategies and the inclusion of TPT in client-centred services, such as differentiated service delivery (DSD) models. Robust collaboration between the HIV and TB programmes represents a unique opportunity to ensure that TB, a preventable and curable condition, is no longer the number one cause of death in PLHIV.