A study has shown that a recently developed test for TB can be used effectively in resource poor settings to rapidly diagnose those infected, including those with multi-drug resistant TB. The findings, published Online First and in an upcoming Lancet , could eventually reduce delays in diagnosis and treatment and thus reduce morbidity and mortality. The study report is authored by Dr Catharina Cora Boehme of FIND (Foundation for Innovative New Diagnostics), Switzerland, and colleagues.
The Xpert MTB/RIF test (Cepheid, Sunnyvale, CA, USA) has been shown to detect tuberculosis and its multi-drug resistant (MDR) form with very high sensitivity and specificity in controlled studies in reference laboratories, but prior to this new work, no performance data existed from district and subdistrict health facilities in tuberculosis-endemic countries. Thus the authors carried out such an analysis.
The study recruited 6648 participants aged 18 years and over 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. The authors compared one-off direct MTB/RIF testing in nine microscopy laboratories adjacent to study sites with the standard TB diagnostic methods of 2 sputum smears and 1 cultures, dependent on site, and drug-susceptibility testing.
A single direct MTB/RIF test detected 933 (90%) of 1033 culture-confirmed cases of tuberculosis, compared with 699 (67%) of 1041 for microscopy. MTB/RIF test sensitivity* was 77% in smear-negative, culture-positive patients (296 of 385 samples), and 99% specific. Sensitivity for rifampicin resistance was 94% (236 of 250) and specificity was 98% (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, compared with 1 day for microscopy, 30 days for solid culture, and 16 days for liquid culture. Median time to detection of resistance was 20 days (10) for line-probe assay and 106 days (30�) for conventional drug susceptibility testing. Use of the MTB/RIF test reduced median time to treatment for smear-negative tuberculosis from 56 days to 5 days.
The authors say: "Our study confirms the sensitivity of the MTB/RIF test for smear-positive and smear-negative tuberculosis, when undertaken in routine microscopy centres, and showed reduced**, but good, performance for detection of rifampicin resistance. Furthermore, we suggest the MTB/RIF test can provide a substantially reduced time to detection and treatment for smear-negative tuberculosis."
They conclude: "Our findings suggest that decentralised MTB/RIF test implementation is feasible and could lead to an improvement in tuberculosis care and control. Any improvement will require increased detection oftuberculosis and multidrug-resistant-tuberculosis to coincide with scale-up of first-line, and more importantly, second-line treatment. Whether early and appropriate treatment after MTB/RIF testing can reduce tuberculosis-associated morbidity and mortality, and its effect on transmission, needs to be established."
In a linked Comment, Dr Katharina Kranzer, London School of Hygiene and Tropical Medicine, UK, says: "Although we acknowledge the achievement of the MTB/RIF test, a diagnostic test with only 90% sensitivity for a potentially life-threatening disease is far from perfect. The device is still not the point-of-care test that health providers desire: it needs electricity, operating temperatures of less than 30°C, and takes about 2 h to process a sample. The instrument and the supplies are too expensive for most countries with a high burden of tuberculosis."
She adds: "Scaling up of testing needs to be accompanied by a rapid increase in access to treatment. In the past decade, about 5 million people developed drug-resistant tuberculosis but less than 1% had access to appropriate treatment, and 1•5 million died. The positive results with the MTB/RIF test are an urgent wake-up call to the international community that a substantial increase in capacity to manage multidrug-resistant tuberculosis at scale is needed, together with major improvements in the availability of high-quality affordable treatment."
Dr Catharina Cora Boehme, FIND (Foundation for Innovative New Diagnostics), contact via Dr Mark Perkins, FIND (Foundation for Innovative New Diagnostics), Switzerland. T) +41 79 745 1467 E) mark.perkins@finddiagnostics.org / catharina.boehme@finddiagnostics.org
Dr Katharina Kranzer, London School of Hygiene and Tropical Medicine, UK. E) katharina.kranzer@lshtm.ac.uk
Note to editors: *sensitivity=true positive rate and specificity=true negative rate
**reduced performance compared with previous reference laboratory results
The Lancet