Does using the Xpert MTB/RIF diagnostic test instead of smear microscopy when evaluating people for tuberculosis reduce death and successful treatment completion?

What is the aim of the review?

Tuberculosis (TB) is a bacterial infection that is spread by inhaling tiny droplets from the coughs or sneezes of an infected person. It mainly affects the lungs, but it can affect any part of the body. Tuberculosis can usually be cured by taking anti-tuberculosis antibiotics for six months. Some bacteria are resistant , and then need to be treated with combinations of different antibiotics. Many countries use the Xpert MTB/RIF test to diagnose tuberculosis. We wanted to find out if using this test affected health outcomes, such as death or successful treatment in people suspected of having tuberculosis.

What was studied in this review?

A rapid, accurate diagnosis of tuberculosis ensures people who are ill start taking the right antibiotics as soon as possible. This might reduce the number of people dying, but also, if rifampicin-resistant tuberculosis is detected early, they are more likely to get appropriate treatment. It also helps ensure people who do not have tuberculosis are not treated unnecessarily.

The Xpert MTB/RIF test is an automated molecular test, commonly used to identify tuberculosis and rifampicin resistance at the same time, in less than two hours. The World Health Organization (WHO) recommends using the Xpert MTB/RIF test to diagnose tuberculosis instead of smear microscopy – using a microscope to look for bacteria in samples of sputum (a mixture of saliva and mucus, coughed up from the lungs). This review investigates whether using Xpert MTB/RIF instead of microscopy improves health outcomes.

What are the main results of the review?

We searched for studies that assessed health outcomes in people who had sought treatment and were suspected of having tuberculosis and who were diagnosed using either the Xpert MTB/RIF test or smear microscopy. We found 12 relevant studies. Eight studies included only adults; four included people of all ages. Ten studies took place in sub-Saharan Africa, one in Brazil, and one in Indonesia. The studies followed people for between two months and two years. 

An effect of using the Xpert MTB/RIF test to diagnose tuberculosis, compared with smear microscopy, could not be ruled in or out a for the numbers of people who:

· died (5 studies; 10,409 people);
· were successfully treated (3 studies; 4802 people);
· died within six months (3 studies; 8143 people); or
· were treated for tuberculosis (5 studies; 8793 people).

Compared with smear microscopy, use of the Xpert MTB/RIF test probably:

· reduced the number of HIV-positive people who died during follow-up (5 studies; 1789 people);
· increased the number of people with confirmed tuberculosis who started treatment (3 studies; 1217 people); and
· increased the number of treated people who had a confirmed diagnosis of tuberculosis (6 studies; 2068 people).

None of the studies reported people's satisfaction, or the number of visits before tuberculosis was diagnosed. Only one study looked at the treatment of tuberculosis resistant to rifampicin.

Key messages

The results showed that there was a beneficial effect of Xpert MTB/RIF for some health outcomes, and inconclusive results (where an effect could not be ruled in or out) for others.

Together, these findings can help inform decisions about the uptake of Xpert MTB/RIF, alongside information on cost-effectiveness and implementation.

How up to date is this review?

We included studies published to 24 July 2020.

Authors' conclusions: 

We were unable to confidently rule in or rule out the effect on all-cause mortality of using Xpert MTB/RIF rather than smear microscopy. Xpert MTB/RIF probably reduces mortality among participants known to be infected with HIV. We are uncertain whether Xpert MTB/RIF has a modest effect or not on the proportion treated or, among those treated, on the proportion with a successful outcome. It probably does not have a substantial effect on these outcomes. Xpert MTB/RIF probably increases both the proportion of treated participants who had bacteriological confirmation, and the proportion with a laboratory-confirmed diagnosis who were treated. These findings may inform decisions about uptake alongside evidence on cost-effectiveness and implementation.

Read the full abstract...
Background: 

The World Health Organization (WHO) recommends Xpert MTB/RIF in place of smear microscopy to diagnose tuberculosis (TB), and many countries have adopted it into their diagnostic algorithms. However, it is not clear whether the greater accuracy of the test translates into improved health outcomes.

Objectives: 

To assess the impact of Xpert MTB/RIF on patient outcomes in people being investigated for tuberculosis.

Search strategy: 

We searched the following databases, without language restriction, from 2007 to 24 July 2020: Cochrane Infectious Disease Group (CIDG) Specialized Register; CENTRAL; MEDLINE OVID; Embase OVID; CINAHL EBSCO; LILACS BIREME; Science Citation Index Expanded (Web of Science), Social Sciences citation index (Web of Science), and Conference Proceedings Citation Index - Social Science & Humanities (Web of Science). We also searched the WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and the Pan African Clinical Trials Registry for ongoing trials.

Selection criteria: 

We included individual- and cluster-randomized trials, and before-after studies, in participants being investigated for tuberculosis. We analysed the randomized and non-randomized studies separately. 

Data collection and analysis: 

For each study, two review authors independently extracted data, using a piloted data extraction tool. We assessed the risk of bias using Cochrane and Effective Practice and Organisation of Care (EPOC) tools. We used random effects meta-analysis to allow for heterogeneity between studies in setting and design.  The certainty of the  evidence in the randomized trials was assessed by GRADE.

Main results: 

We included 12 studies: eight were randomized controlled trials (RCTs), and four were before-and-after studies. Most included RCTs had a low risk of bias in most domains of the Cochrane 'Risk of bias' tool.

There was inconclusive evidence of an effect of Xpert MTB/RIF on all-cause mortality, both overall (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.75 to 1.05; 5 RCTs, 9932 participants, moderate-certainty evidence), and restricted to studies with six-month follow-up (RR 0.98, 95% CI 0.78 to 1.22; 3 RCTs, 8143 participants; moderate-certainty evidence). There was probably a reduction in mortality in participants known to be infected with HIV (odds ratio (OR) 0.80, 95% CI 0.67 to 0.96; 5 RCTs, 5855 participants; moderate-certainty evidence).

It is uncertain whether Xpert MTB/RIF has no or a modest effect on the proportion of participants starting tuberculosis treatment who had a successful treatment outcome (OR) 1.10, 95% CI 0.96 to 1.26; 3RCTs, 4802 participants; moderate-certainty evidence).

There was also inconclusive evidence of an effect on the  proportion of participants who were treated for tuberculosis (RR 1.10, 95% CI 0.98 to 1.23; 5 RCTs, 8793 participants; moderate-certainty evidence).

The proportion of participants treated for tuberculosis who had bacteriological confirmation was probably higher in the Xpert MTB/RIF group (RR 1.44, 95% CI 1.29 to 1.61; 6 RCTs, 2068 participants; moderate-certainty evidence). The proportion of participants with bacteriological confirmation who were lost to follow-up pre-treatment was probably reduced (RR 0.59, 95% CI 0.41 to 0.85; 3 RCTs, 1217 participants; moderate-certainty evidence).

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