Use of Xpert MTB/RIF in Decentralized Public Health Settings and Its Effect on Pulmonary TB and DR-TB Case Finding in India

Abstract

BackgroundXpert MTB/RIF, the first automated molecular test for tuberculosis, is transforming the diagnostic landscape in high-burden settings. This study assessed the impact of up-front Xpert MTB/RIF testing on detection of pulmonary tuberculosis (PTB) and rifampicin-resistant PTB (DR-TB) cases in India.MethodsThis demonstration study was implemented in 18 sub-district level TB programme units (TUs) in India in diverse geographic and demographic settings covering a population of 8.8 million. A baseline phase in 14 TUs captured programmatic baseline data, and an intervention phase in 18 TUs had Xpert MTB/RIF offered to all presumptive TB patients. We estimated changes in detection of TB and DR-TB, the former using binomial regression models to adjust for clustering and covariates.ResultsIn the 14 study TUs, which participated in both phases, 10,675 and 70,556 presumptive TB patients were enrolled in the baseline and intervention phase, respectively, and 1,532 (14.4%) and 14,299 (20.3%) bacteriologically confirmed PTB cases were detected. The implementation of Xpert MTB/RIF was associated with increases in both notification rates of bacteriologically confirmed TB cases (adjusted incidence rate ratio [aIRR] 1.39; CI 1.18-1.64), and proportion of bacteriological confirmed TB cases among presumptive TB cases (adjusted risk ratio (aRR) 1.33; CI 1.6-1.52). Compared with the baseline strategy of selective drug-susceptibility testing only for PTB cases at high risk of drug-resistant TB, Xpert MTB/RIF implementation increased rifampicin resistant TB case detection by over fivefold. Among, 2765 rifampicin resistance cases detected, 1055 were retested with conventional drug susceptibility testing (DST). Positive predictive value (PPV) of rifampicin resistance detected by Xpert MTB/RIF was 94.7% (CI 91.3-98.1), in comparison to conventional DST.ConclusionIntroduction of Xpert MTB/RIF as initial diagnostic test for TB in public health facilities significantly increased case-notification rates of all bacteriologically confirmed TB by 39% and rifampicin-resistant TB case notification by fivefold.

Unsuccessful Xpert® MTB/RIF results: the Nigerian experience

“…The patient population screened, which comprised presumptive drug-resistant cases and patients with human immunodeficiency virus with TB symptoms, contributed to the high RR-TB detection rate. The main impetus was the timely detection of multidrug-resistant TB, [16][17][18][19] as RMP resistance is a surrogate for isoniazid resistance. 20,21 The key lesson learnt from the Xpert roll-out was that access to diagnosis is not the only indicator for measuring successful implementation; the rate of unsuccessful tests (which add no value to treatment) is also an important indicator of the effectiveness of Xpert implementation over time.…”

Understanding the incremental value of novel diagnostic tests for tuberculosis

“…These data would enable us to evaluate the incremental number of transmissions that a novel test might be able to avert, relative to the existing standard of care. A series of recent high-quality studies suggests that, when patients present with symptoms that are highly suggestive of TB in upper-middle income settings (for example, South Africa and Brazil), the probability of empirical diagnosis is reasonably high [8][9][10][11] -but that a large number of people may be presenting to care with a cough without TB ever being considered 8 . Such studies are crucial to understand the likely diagnostic gaps for TB, but unfortunately, very few such analyses have been performed in settings with fewer resources (for example, most of sub-Saharan Africa 73,74 and Southeast Asia) where empirical diagnosis rates (and the capacity to implement novel diagnostic tests) may be much lower.…”

“…Nevertheless, the link between improved diagnostic sensitivity and better TB detection remains uncertain. Studies [8][9][10][11] in different settings have found little or no change in the number of pulmonary TB diagnoses or deaths when comparing sputum smear microscopy and Xpert MTB/RIF, a more sensitive molecular test 12 . This result may reflect high levels of empirical treatment among people who test negative [13][14][15] .…”

Bottom-up or top-down: unit cost estimation of tuberculosis diagnostic tests in India

“…4,5 For an economic analysis of the potential scale-up of Xpert testing in India, unit cost estimates of Xpert, sputum smear microscopy (SSM), as well as of other commonly used tests to diagnose drug-resistant TB in India, were required. Earlier TB diagnostic costing studies in India were from limited settings and conducted during the early stages of Xpert demonstration studies.…”