Near point-of-care nucleic acid amplification tests (NPOC- NAATs) as a new diagnostic class for diagnosis of TB using sputum and tongue swabs
Near point-of-care nucleic acid amplification tests (NPOC-NAATs) are swab-based molecular tests for TB detection that can produce results from a primary sputum or tongue swab sample in less than one hour using instruments that can be battery operated and do not require specialized infrastructure for use or storage.
These tests can be done in basic peripheral laboratories, such as those that perform smear microscopy, and health clinics, mobile units, or community sites that do not have laboratories. They can be performed by health care workers with basic technical skills because they do not require laboratory methods like precision pipetting. However, like smear microscopy, this class of tests does not incorporate rifampicin-resistance detection and therefore requires reflex testing with a complementary solution for drug-resistance determination.
More information on the defining characteristics of TB NPOC-NAATs may be found here.
In adults and adolescents with signs and symptoms of pulmonary TB or who screen positive for pulmonary TB, NPOC-NAATs on sputum should be used as initial diagnostic tests for TB rather than smear microscopy (strong recommendation, moderate certainty of evidence);
When sputum cannot be obtained, NPOC-NAATs on tongue swabs should be used as initial diagnostic tests for TB (strong recommendation, moderate certainty of evidence).
Remarks
- The term “person screened positive” refers to a person in whom screening yielded a positive result (1).
- Evidence was available for both expectorated and induced sputum.
- Sputum remains the preferred sample type and should be collected and tested whenever possible, given improved diagnostic accuracy over tongue swabs.
- Tongue swabs may be collected by trained personnel or self-collected with guidance from trained personnel.
- This recommendation applies to adults and adolescents living with HIV, although evidence for this group was limited, and no evidence was available for people with advanced HIV disease or severe illness. However, wherever available, concurrent testing with an LC-aNAAT and LF-LAM is the preferred testing strategy for people living with HIV. In the context of concurrent testing, where LC-aNAATs are not available, NPOC-NAATs may be used concurrently with LF-LAM; where a respiratory sample is unobtainable, a tongue swab may be used concurrently with LF-LAM.
- The recommendation was extrapolated to children for use with sputum (expectorated or induced) based on data from adults and limited data from children, acknowledging the difficulties of collecting sputum specimens from this population. The recommendation does not apply to the use of paediatric samples other than sputum (i.e., BAL, gastric aspirates, nasopharyngeal aspirates), tongue swabs, or stool (no data). Wherever available, concurrent testing with LC-aNAATs on respiratory and stool samples (and LF-LAM among those that are HIV positive) is the preferred testing strategy for children.
- As NPOC-NAATs do not yet provide rifampicin-resistance results, remaining or new samples from all positive tests should be referred for DST.
Because use of this diagnostic class is decentralized to peripheral and non-lab settings, engagement of civil society and community organizations for early communication, demand creation, delivery and monitoring are essential. National programmes should consider developing context-specific plans and communication strategies for NPOC-NAAT testing in new or peripheral areas in close collaboration with civil society.
Description of the first-in-class near point-of-care test
The product for which eligible data met the performance criteria to establish the class of NPOC-NAATs was the MTBC Nucleic Acid Test Card from Pluslife in Guangzhou, China. For this test, swabs of sputum or tongue are prepared, inserted into a sample tube that is pre-filled with lysis buffer and beads, and the tube is vortexed with heat on a ThermoLyse instrument for mechanical, chemical, and thermal lysis. The lysed sample solution tube is then inverted and squeezed to drop the lysis solution into the MTBC Nucleic Acid Test Card to run on the Pluslife MiniDock amplification instrument. Both instruments can be operated on standard currents or with battery power with results available in approximately 30 minutes, reported through built-in indicator lights on the MiniDock instrument or through an optional laptop with software and can be downloaded or transmitted by Bluetooth from the instrument for electronic sharing.
This test is currently available from The Global Fund to Fight AIDS, Tuberculosis and Malaria and the Stop TB Partnership Global Drug Facility at $3.60 USD per test and $355 USD per instrument pair with one-year warranties (2).
Extrapolation to other brand-specific tests cannot be made, and any new in-class technologies or new indications for technologies currently included in the class will need to be evaluated by WHO Prequalification. A prequalification process for this and other classes of TB NAAT products is available to support market expansion and ensure quality of WHO-recommended technologies.
Overview of evidence and judgements
The available evidence on test accuracy included 5 studies (9 countries, 3291 participants) that evaluated expectorated and induced sputum, and 6 studies (10 countries, 3335 participants) that evaluated tongue swabs against a microbiological reference standard.
Evidence on testing costs included one study on the use of NPOC-NAATs on sputum, and 2 studies on tongue swabs. Given limited published evidence on cost-effectiveness, a modelling study was carried out to support the GDG. Lastly, evidence was assessed on NPOC-NAAT end user perspectives from a mixed method review (85 studies, 129 countries) reported from 2020 to 2025 on tongue or oral swabs for diagnosing TB and other infectious diseases. Additional evidence was gathered through in-depth interviews with TB programme officers, implementers, lab managers and researchers, a focus group discussion with people with lived experience of TB and an online survey of national TB programme officers, implementers, lab managers and researchers.
Compared with smear microscopy, the GDG judged the use of NPOC-NAATs on sputum to be very accurate (summary sensitivity of 85.4% (95% CI: 82.2–88.1) and specificity of 97.6% (95% CI: 96.9–98.1)), and NPOC-NAATs on tongue swabs to be accurate irrespective of whether swabs were self-collected or collected by health-care workers (summary sensitivity of 76.4% (95% CI: 71.2–80.9) and summary specificity of 99.2% (95% CI: 98.7–99.5)). Among adults and adolescents living with HIV (5 studies, 506 participants), the summary sensitivity of sputum testing was 79.2% (95% CI: 68.7-86.9) and the summary specificity was 96.7% (95% CI: 94.6-98.1). Among adults and adolescents living with HIV tested with tongue swabs (4 studies with 483 participants), the summary sensitivity was 69.3% (95% CI: 58.1-78.7) and the summary specificity was 99.5% (95% CI: 98.1-99.9). Diagnostic accuracy assessment was based on a majority of evidence from individuals that were able to produce sputum. For both respiratory samples and tongue swabs, sensitivity among patients with very low or trace Xpert MTB/RIF Ultra results was much lower and highly variable, although the number of participants in these categories was small.
Unit NPOC-NAAT costs moderately increased compared to smear microscopy but were approximately half of the cost of LC-aNAATs. Compared with smear microscopy, NPOC-NAATs on sputum were found to likely be highly cost-effective. Compared to LC-aNAATs, NPOC-NAATs on tongue swabs were cost saving but less effective. The GDG also judged that NPOC-NAATs on either sputa or tongue swabs would increase equity, be acceptable to end users, and be feasible to implement.
References
- Having a positive result of a test, examination or other procedure used to distinguish people with a high likelihood of having TB disease from people who are highly unlikely to have TB. At present, the following tests are WHO-recommended as the screening tests: chest radiography (chest X-ray; CXR) with or without computer-aided detection (CAD), C-reactive protein (CRP) in people living with HIV, and molecular WHO-recommended rapid diagnostic test for TB (mWRD) (read more: WHO consolidated guidelines on tuberculosis: module 2: screening: systematic screening for tuberculosis disease).
- Stop TB Partnership Global Drug Facility Diagnostics, Medical Devices, and Other Health Products Catalogue. GDF Product Catalog | Stop TB Partnership.