The first randomised trial to measure the impact of the rapid Xpert MTB/RIF test for tuberculosis (TB) in a real-life clinical setting finds that it can be accurately performed by a non-specialist with minimal training, improves same-day diagnosis and time to starting treatment, and increases the number of people who start treatment after testing positive on day 1 by 50%, compared with conventional TB diagnostics.
"Despite already being rolled-out in many countries, our study is the first to look at the feasibility of the Xpert test in a real-life clinical setting in southern Africa", explains study leader Professor Keertan Dheda from the Department of Medicine, University of Cape Town in South Africa in The Lancet.
"Although earlier diagnosis by the Xpert test did not reduce overall severity of TB-related illness, and moreover did not reduce the overall number TB cases treated over the course of the study, it has substantial benefits over smear microscopy including improved rates of same-day diagnosis and reducing treatment drop-out."*
TB diagnosis still relies mainly on the insensitive, time-consuming, and century-old combination of sputum smear microscopy and chest x-ray that miss 40 - 60% of cases. Additionally, up to 40% of people who test positive for TB do not return for their test results or begin treatment.
In 2011, WHO endorsed the use of the Xpert automated test that can show a result within 2 hours, for people with suspected multi-drug resistant TB and TB complicated by HIV infection. Although its accuracy has been well validated, until now, its viability outside a lab delivered by clinical staff with minimal training has not been assessed.
In this study, Dr Grant Theron and co-workers led by Professor Dheda investigated the feasibility of the Xpert test (accuracy, failure rates, operator adherence, and user appraisal) when performed by a nurse (who received 1 day of training) and its effect on patient health compared with smear microscopy in five primary health-care facilities in South Africa, Zimbabwe, Zambia, and Tanzania - countries with high rates of TB and HIV.
They randomly assigned 758 adults with suspected TB to same-day smear microscopy (182 culture positive) and 744 to Xpert testing (185 culture positive). TB-related illness was assessed in culture-positive patients at the start of the study and 2 months and 6 months after starting treatment using scoring systems that measure quality of life, and signs and symptoms of TB.
Despite a longer delay to treatment in the microscopy group, no difference in the severity TB-related illness, which correlates well with longer term prognosis, was noted after 2 months and 6 months between the groups. However, the Xpert test diagnosed more culture-confirmed cases of TB (154 of 185 [83%]) compared to microscopy (91 of 182 [50%]), with improved same-day rates of treatment initiation (52% vs 35%), and halved drop-out rates (people who tested positive but did not start treatment; 15% vs 8%).
According to Professor Dheda, "Whilst Xpert may not be the ideal point of care TB test in particularly poorly resourced settings, in countries like South Africa where the clinic infrastructure is relatively good, rates of drug-resistant TB are high, and patient drop-out are significant problems, within clinic placement of Xpert in TB hotspots might be appropriate and enable earlier diagnosis of drug-resistant TB thus likely reducing community-based transmission. Nevertheless, prevention of TB and adherence to TB treatment is critical and remains a major priority."*
Writing in a linked Comment, Christian Wejse from Aarhus University in Denmark questions whether, in light of these findings, the substantial financial cost of Xpert roll-out provides value for money, "Placing very expensive equipment in health-care facilities in rural Africa that might have no electricity and poorly trained, underpaid staff is going to be a difficult undertaking. Are the incremental gains in same-day diagnosis and treatment initiation, as well as reduced loss to follow-up, enough to justify this investment?"
He adds, "At a cassette cost of US$10 (reduced price for low-resource settings), testing large numbers of people with suspected tuberculosis will put substantial pressure on already resource-limited tuberculosis programmes in which the drugs for treatment might not always be available. Hence, the provocative question raised by this study is whether tuberculosis elimination is most likely to be advanced by distributing GeneXpert machines to all peripheral health facilities in the world, or by investing the same amount in ensuring that health facilities have the set-up available in this study - ie, well trained and paid staff, electricity, and reagents."