Key messages
– Truenat MTB Plus was more accurate than Truenat MTB for detecting pulmonary tuberculosis. Truenat MTB misidentified many people as having tuberculosis when they did not, which raises concern.
– Xpert Ultra was more accurate than Truenat MTB.
– Evidence on the accuracy of Truenat assay for detecting rifampicin was limited.
What is pulmonary tuberculosis?
Pulmonary tuberculosis is a lung disease caused by a bacterium (a germ) that spreads through the air via droplets from an infected person. In early stages, it remains dormant (does not multiply) and presents symptoms like fever, cough, weight loss, and night sweats. When a person coughs and produces sputum (a mix of saliva and mucus) or blood-stained sputum, they are advised to visit a healthcare professional
Drug-resistant tuberculosis is caused by bacteria that are not killed by at least one effective antibacterial medicine (for example, isoniazid or rifampicin) used to treat tuberculosis (called drug resistance). Delay in diagnosis of drug-resistant tuberculosis may increase spread from one person to another, and lead to further drug resistance. Diagnosis relies on demonstrating the presence of the bacteria or its DNA (which carries the genetic material needed for the bacteria to multiply) in a sputum sample. There are several ways of diagnosing tuberculosis. Examining a sputum sample under a microscope is easy and cheap, but it needs the presence of many bacteria so is not useful in early disease. Another way is to grow bacteria in a laboratory, but this takes weeks and is more expensive, particularly for poorer countries. The most-recent way is using a simple, quick, portable, and cost-effective assay to detect the bacteria within hours. These may be useful in poorer countries. While culture is the best way to confirm the disease, early and accurate identification is essential to start treatment and prevent debilitating and fatal illness. Assays would do this.
Why is improving diagnosis important?
According to the World Health Organization (WHO), in 2023, 10.8 million people had tuberculosis, and 1.25 million people died. The number of people with tuberculosis keeps increasing. It is crucial to have a test that accurately determines whether the disease is present (called a true positive) or absent (a true negative) without producing errors (like claiming the disease is present when it is not (false positive), claiming it is not there when it is (false negative), or invalid or inconclusive results). False-positive results cause unnecessary anxiety, and people will be monitored, requiring time and resources. These people may also be started on treatment with severe unwanted effects. False-negative results may miss cases, spreading disease in the general population. People with false-negative results may develop severe forms of tuberculosis with fatal outcomes due to delayed diagnosis and treatment.
What did we want to find out?
We wanted to assess the accuracy of three Truenat assays; two for detecting pulmonary tuberculosis (MTB, MTB Plus) and one for detecting rifampicin resistance (MTB RIF Dx) in adults and adolescents (aged 10 years and older) with suspected pulmonary tuberculosis.
What did we do?
We looked for studies assessing the accuracy of Truenat assays and compared them with another assay recommended by WHO (Xpert Ultra). The results of these tests were verified against culture for detecting pulmonary tuberculosis and tested for resistance to rifampicin, the most common antibiotic used to treat tuberculosis.
What did we find?
We found six studies (4081 people) for Truenat MTB, four studies (3073 people) for Truenat MTB Plus, and two studies (966 people) for Truenat MTB RIF Dx. Three studies also evaluated Xpert Ultra in addition to Truenat.
For the Truenat MTB assay, for 1000 people where 100 have tuberculosis confirmed by culture, 214 will be Truenat MTB positive. Of these, the assay will correctly identify 88 people with tuberculosis, but will incorrectly identify 126 people as having tuberculosis when they do not (false positives). Similarly, 786 will be Truenat MTB negative. Of these, the assay will identify 774 people as not having tuberculosis, of whom 12 will actually have tuberculosis (false negatives) and be missed.
For the Truenat Plus assay, for 1000 people where 100 have tuberculosis confirmed by culture, 127 will be Truenat MTB Plus positive. Of these, the assay will correctly identify 91 people with tuberculosis, but will incorrectly identify 36 people as having tuberculosis when they do not (false positives). Similarly, 873 will be Truenat MTB Plus negative. Of these, the assay will identify 864 people as not having tuberculosis, of whom nine will actually have tuberculosis (false negatives) and be missed.
For the detection of rifampicin resistance, the evidence was limited.
How confident are we in the results of this review?
We are confident of our results. We included a good number of studies and participants. Overall, the included studies were well conducted.
Who do the results of this review apply to?
The results of this review apply to people with symptoms suggestive of pulmonary tuberculosis.
How up to date is this review?
The review is up to date to 16 October 2023
Truenat MTB Plus had higher sensitivity and specificity than Truenat MTB. The high false-positive rate for Truenat MTB is a concern. The sensitivity of Xpert Ultra was significantly higher than that of Truenat MTB, while specificity was slightly lower. Evidence on the accuracy of Truenat MTB-RIF Dx was limited.
Accurate and rapid diagnosis is crucial for ending the tuberculosis epidemic. Truenat assays are World Health Organization (WHO)-recommended rapid molecular diagnostic tests that detect Mycobacterium tuberculosis complex and rifampicin resistance.
Primary objective
To assess the diagnostic accuracy of Truenat assays (MTB, MTB Plus, and MTB-RIF Dx) for detecting pulmonary tuberculosis and rifampicin resistance in adults and adolescents with presumptive pulmonary tuberculosis.
Secondary objectives
To compare the diagnostic accuracy of Truenat assays and Xpert MTB/RIF Ultra for detecting pulmonary tuberculosis and rifampicin resistance and to investigate potential sources of heterogeneity (e.g. HIV status and smear status).
We searched MEDLINE, Embase, Science Citation Index and Biosis previews, Global Index Medicus, SCOPUS, WHO ICTRP, and ClinicalTrials.gov for published articles and trials in progress on 16and 17 October 2023. We searched ProQuest Dissertations & Theses A&I for dissertations. We contacted tuberculosis experts for ongoing and unpublished studies. A WHO public call for data was made between 30 November 2023 and 15 February 2024.
We included cross-sectional and cohort studies that evaluated Truenat assays in sputum samples from adolescents and adults (aged 10 years and older). The microbiological reference standard for identifying pulmonary tuberculosis is culture. The reference standard for rifampicin resistance is a culture-based drug susceptibility test. Two review authors independently screened titles and abstracts, and assessed the full texts of potentially eligible articles. A third review author resolved any disagreements.
We tailored and applied the QUADAS-2 and QUADAS-C tools to assess the risk of bias and applicability. Two review authors independently extracted data for each included study, and a third review author resolved any disagreements. We performed meta-analyses to estimate summary sensitivities and specificities using a bivariate model. We assessed the certainty of evidence using the GRADEpro GDT tool.
Of nine eligible articles, one contributed two distinct participant cohorts, which we considered as separate studies. Thus, we included 10 studies; three assessed Xpert Ultra. Most studies were set in low- and middle-income countries with a high tuberculosis burden. Six studies (4081 participants, 1379 with tuberculosis) assessed Truenat MTB, and four studies (3073 participants, 750 with tuberculosis) assessed Truenat MTB Plus. Two studies (966 participants, 111 with rifampicin resistance) assessed Truenat MTB-RIF Dx. Overall, the risk of bias in the included studies was low. Three of the 10 studies were judged to have high applicability concern in the patient selection domain.
Detection of pulmonary tuberculosis
The summary sensitivity of Truenat MTB was 87.6% (95% confidence interval (CI) 81.6 to 91.8; high-certainty evidence), and the summary specificity was 86.1% (95% CI 70.1 to 94.3; moderate-certainty evidence).
For Truenat MTB Plus, the summary sensitivity was 90.6% (95% CI 83.7 to 94.8; high-certainty evidence), and the summary specificity was 95.7% (95% CI 94.7 to 96.5; high-certainty evidence).
Based on the three comparative studies, the summary sensitivity of Truenat MTB was lower (81.0%, 95% CI 72.8 to 87.2) than that of Xpert Ultra (93.7%, 95% CI 90.4 to 95.9), while the summary specificity of Truenat MTB (97.0%, 95% CI 91.9 to 98.9) was marginally higher than Xpert Ultra (95.3%, 95% CI 90.9 to 97.7).
Detection of rifampicin resistance
The sensitivities from the two studies were 53% and 85% (moderate-certainty evidence) and specificities were both 97% (high-certainty evidence).