Systematic Review of Pooling Sputum as an Efficient Method for Xpert MTB/RIF Tuberculosis Testing during the COVID-19 Pandemic

Abstract

GeneXpert-based testing with Xpert MTB/RIF or Ultra assays is essential for tuberculosis diagnosis. However, testing may be affected by cartridge and staff shortages. More efficient testing strategies could help, especially during the coronavirus disease pandemic. We searched the literature to systematically review whether GeneXpert-based testing of pooled sputum samples achieves sensitivity and specificity similar to testing individual samples; this method could potentially save time and preserve the limited supply of cartridges. From 6 publications, we found 2-sample pools using Xpert MTB/RIF had 87.5% and 96.0% sensitivity (average sensitivity 94%; 95% CI 89.0%–98.0%) (2 studies). Four-sample pools averaged 91% sensitivity with Xpert MTB/RIF (2 studies) and 98% with Ultra (2 studies); combining >4 samples resulted in lower sensitivity. Two studies reported that pooling achieved 99%–100% specificity and 27%–31% in cartridge savings. Our results show that pooling may improve efficiency of GeneXpert-based testing.

Pooled testing of sputum with Xpert MTB/RIF and Xpert Ultra during tuberculosis active case finding campaigns in Lao People’s Democratic Republic

“…Previous systematic reviews have highlighted that individual and pooled RIF results are often discordant, with pools containing RIF-negative samples often returning RIF-indeterminate pooled results, 19 and our findings are in agreement with these observations. Although samples with pooled RIF results would be routinely confirmed at the time of retesting, the samples of a positive pool to identify the individual MTB-positive samples, it is important to highlight that pooled RIF results are unreliable and should not be used for clinical management.…”

“…This is higher than in PCF studies, where pooling is reported to save up to 40% of cartridges. 19 Cartridge savings are a function of the proportion of people with MTB-positive results and their distribution within the pools. If the proportion positive is low, a low number of pools would need to be retested, resulting in higher cartridge savings.…”

“…If the test is positive, the pool's samples are retested individually to identify the positive sample(s) while if the test is negative, all samples in the pool are considered negative, resulting in 30%-40% savings in Xpert cartridge costs alone depending on the prevalence of TB in the population tested. 19 Therefore, pooling may hold great promise for ACF, but there are few reports of its performance under operational conditions. 20 Here, we report a prospective study to assess the sensitivity and specificity of the pooling method using Xpert MTB/RIF and Xpert-Ultra during intensified case finding interventions, and its potential to increase the affordability of Xpert testing in Lao PDR.…”

“…This procedure combines (or pools) the sputum of several individuals into one pot and tests them together with a single test. If the test is positive, the pool’s samples are retested individually to identify the positive sample(s) while if the test is negative, all samples in the pool are considered negative, resulting in 30%–40% savings in Xpert cartridge costs alone depending on the prevalence of TB in the population tested 19. Therefore, pooling may hold great promise for ACF, but there are few reports of its performance under operational conditions 20…”

The diagnostic accuracy of pooled testing from multiple individuals for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae: a systematic review

“…Laboratory diagnosis of sexually transmitted infections, including human immunodeficiency virus) One strategy to improve access to molecular testing for CT/NG includes pooling specimens to reduce costs and improve efficiency. This strategy has been implemented previously for pathogens such as Mycobacterium tuberculosis (Cuevas et al 2021) and SARS-CoV-2. (Burdett et al 2021) Indeed, pooled testing increases the number of people tested with the same budget.…”