Key message: Xpert MTB/RIF is a diagnostic test which can quickly detect pulmonary tuberculosis and rifampicin resistance in adults, with a high degree of accuracy and without the need for laboratory facilities, allowing Something done with the aim of improving health or relieving suffering. For example, medicines, surgery, psychological and physical therapies, diet and exercise changes. to be started quickly.
Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis, is spread from person to person through the air and most commonly affects the lungs (pulmonary tuberculosis or PTB) but may affect any other organ or tissue (extrapulmonary tuberculosis). Tuberculosis has been with us since ancient times and is now the most common infection-related cause of death worldwide, as well as one of the top 10 causes of death overall (WHO Global TB Report 2018). In 2017, 10 million people developed TB (of whom 9% also had HIV) and 1.6 million died from it, yet it’s a disease that is largely curable if detected early and effectively treated (WHO Global TB Report 2018). Ending the TB epidemic by 2030 is one of the health targets of the Sustainable Development Goals.
Improving TB detection
Quickly and accurately detecting TB, including drug-resistant TB and smear-negative TB (which gives a negative result on sputum smear microscopy), is really important for improving patient Outcomes are measures of health (for example quality of life, pain, blood sugar levels) that can be used to assess the effectiveness and safety of a treatment or other intervention (for example a drug, surgery, or exercise). In research, the outcomes considered most important are ‘primary outcomes’ and those considered less important are ‘secondary outcomes’.. Many people with TB remain undiagnosed and, although rates are improving, many are not tested for tuberculosis drug resistance. Drug-resistant TB, including multidrug-resistant TB (MDR-TB), defined as resistance to at least isoniazid and rifampicin (anti-TB drugs), is a major problem. People with drug-resistant TB can pass on the infection to others.
Mycobacterial culture, generally considered the best available reference standard (test) for TB diagnosis and the first step in detecting drug resistance, is a fairly complex and slow procedure, needing specialized laboratories and highly skilled staff. The World Health Organization recommends a simple test – Xpert MTB/RIF, and the newest version Xpert Ultra, that within two hours can detect TB and rifampicin resistance in someone with TB symptoms. As well as being quick, the test uses an automated process in a single, self-contained unit, the GeneXpert cartridge, which doesn’t need to be done in a laboratory.
The latest evidence
Two important things to know about a diagnostic test are how sensitive it is – that is, how well it identifies people who have the disease of interest, and how specific – how good it is at identifying those who are free of the disease. A Cochrane Review looking at the diagnostic accuracy of this test previously found Xpert MTB/RIF to be a sensitive and specific test for pulmonary tuberculosis and rifampicin resistance. It has now been updated for a forthcoming WHO policy review. The authors were able to add 77 new studies, bringing the total to 95. 86 studies (42,091 participants) evaluated Xpert MTB/RIF for tuberculosis and 57 studies (8287 participants) for rifampicin resistance. One An investigation of a healthcare problem. There are different types of studies used to answer research questions, for example randomised controlled trials or observational studies. compared Xpert MTB/RIF with Xpert Ultra on the same A person who takes part in a trial, often but not necessarily a patient. specimen. Most studies had low A way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. of Any factor, recognised or not, that distorts the findings of a study. For example, reporting bias is a type of bias that occurs when researchers, or others (e.g. drug companies) choose not report or publish the results of a study, or do not provide full information about a study.. Their findings are consistent with those reported previously.
There is high-certainty evidence that Xpert MTB/RIF is sensitive and specific for diagnosing pulmonary TB and rifampicin resistance.
- Pulmonary TB detection: Xpert MTB/RIF pooled A measure of a screening or diagnostic test’s ability to correctly detect people who have the disease. and A measure of a screening or diagnostic test’s ability to correctly identify people who do not have the disease. (95% credible Interval (CrI)) were 85% (82% to 88%) and 98% (97% to 98%), (70 studies, 37,237 unselected participants).
- Rifampicin resistance detection: Xpert MTB/RIF pooled sensitivity and specificity (95% Crl) were 96% (94% to 97%) and 98% (98% to 99%), (48 studies, 8020 participants).
Xpert MTB/RIF is more sensitive for TB in smear-positive than smear-negative people and HIV-negative than HIV-positive people.
- Xpert MTB/RIF pooled sensitivity was 98% (97% to 98%) in smear‐positive and 67% (62% to 72%) in smear‐negative, culture‐positive participants, (45 studies).
- Xpert MTB/RIF pooled sensitivity was 88% (83% to 92%) in HIV‐negative and 81% (75% to 86%) in HIV‐positive participants; specificities were similar 98% (97% to 99%), (14 studies).
Compared with Xpert MTB/RIF, Xpert Ultra has higher sensitivity and lower specificity for TB and similar sensitivity and specificity for rifamipicin resistance (one study; The certainty (or quality) of evidence is the extent to which we can be confident that what the research tells us about a particular treatment effect is likely to be accurate. Concerns about factors such as bias can reduce the certainty of the evidence. Evidence may be of high certainty; moderate certainty; low certainty or very-low certainty. Cochrane has adopted the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation) for assessing certainty (or quality) of evidence. Find out more here: https://training.cochrane.org/grade-approach evidence).
- Xpert Ultra sensitivity (95% confidence interval (CI)) was 88% (85% to 91%) versus Xpert MTB/RIF 83% (79% to 86%). Xpert Ultra specificity was 96% (94% to 97%) versus Xpert MTB/RIF 98% (97% to 99%).
- Xpert Ultra sensitivity (95% CI) was 95% (90% to 98%) versus Xpert MTB/RIF 95% (91% to 98%); Xpert Ultra specificity was 98% (97% to 99%) versus Xpert MTB/RIF 98% (96% to 99%).
Impact on health outcomes?
Early detection of TB and rifampicin resistance needs to be followed by appropriate treatment for there to be better outcomes for patients. The review authors could not systematically evaluate the impact of Xpert MTB/RIF on health outcomes in people with TB as part of this review but there is another Cochrane Review under way that is aiming to do this.
Detection of TB and rifampicin resistance in children
A new Cochrane Review Xpert MTB/RIF and Xpert MTB/RIF Ultra assays for active tuberculosis and rifampicin resistance in children has now been published (August 2020).
Special Collection on diagnosing tuberculosis
Don’t miss this Cochrane Special Collection: Diagnosing tuberculosis, which includes Cochrane Reviews are systematic reviews. In systematic reviews we search for and summarize studies that answer a specific research question (e.g. is paracetamol effective and safe for treating back pain?). The studies are identified, assessed, and summarized by using a systematic and predefined approach. They inform recommendations for healthcare and research. and other In systematic reviews we search for and summarize studies that answer a specific research question (e.g. is paracetamol effective and safe for treating back pain?). The studies are identified, assessed, and summarized by using a systematic and predefined approach. They inform recommendations for healthcare and research., and highlights how Cochrane Reviews are systematic reviews. In systematic reviews we search for and summarize studies that answer a specific research question (e.g. is paracetamol effective and safe for treating back pain?). The studies are identified, assessed, and summarized by using a systematic and predefined approach. They inform recommendations for healthcare and research. contributes to the wider landscape of TB evidence and guidelines. The Collection also describes key WHO guidelines on TB diagnostics, and their underpinning systematic reviews.
This blog was substantially revised on 12 July 2019 and last updated on 28 August 2020.