Rapid Molecular Diagnosis of Pulmonary Tuberculosis in Adults and Children Using Oral Swabs

The World Health Organization (WHO) has proposed oral swabs as an alternative to traditional sputum sampling for tuberculosis (TB) detection, particularly in populations where obtaining sputum is challenging. Oral swabs also hold promise as a sampling method for active community-based screening. The process of using oral swabs for TB diagnosis involves multiple stages: sampling, processing, and analysis. In the latest edition of the "Tuberculosis Window" column by Shenzhen Third Hospital, Professor Lu Shuihua’s team shared a systematic review published in The Lancet Global Health. This review synthesizes recent literature on oral swab-based TB diagnosis, evaluates the diagnostic accuracy of different swab types, and analyzes factors influencing sensitivity and specificity to guide future optimization of oral swab diagnostics.

Study Overview

Tuberculosis, caused by Mycobacterium tuberculosis, remains a leading cause of infectious disease mortality. In 2022, 7.5 million people were diagnosed with TB, yet only 63% of treated patients received microbiological confirmation. The WHO recommends rapid molecular diagnostics for TB screening in symptomatic adults and children. While sputum-based molecular tests like Xpert MTB/RIF and Xpert MTB/RIF Ultra demonstrate high sensitivity, their utility is limited in populations with low sputum production, such as individuals with weak cough reflexes, HIV co-infections, or children under five. To improve accessibility, oral swabs have emerged as a novel diagnostic specimen. The WHO’s recommendation for oral swab-based TB testing underscores the need to standardize sampling, processing, and analysis protocols, as variations in swab type, collection site, processing methods, and nucleic acid amplification tests (NAATs) may impact diagnostic accuracy. This systematic review evaluates existing evidence on oral swabs, identifies factors affecting performance, and proposes strategies to optimize sensitivity.

Figure 1. Factors influencing the sensitivity and specificity of oral swab-based TB diagnosis.

Literature Screening Process

A comprehensive search was conducted across eight databases (MEDLINE, Embase, Scopus, Science Citation Index, medRxiv, bioRxiv, Global Index Medicus, Google Scholar) from 2000 to July 5, 2022, using keywords: ("Mycobacterium tuberculosis" OR "tuberculosis" OR "TB" OR "pulmonary tuberculosis") AND ("oral swab" OR "tongue swab*" OR "buccal swab*")*. After removing 415 duplicates and excluding 509 records based on title/abstract screening, 41 full-text articles were assessed. One study was excluded due to inaccessibility, leaving 20 studies from 16 publications for inclusion. These studies spanned eight countries: South Africa (7), Peru (5), Uganda (3), South Korea (1), Kenya (1), Brazil (1), China (1), and Moldova (1), involving 3,083 participants.

Figure 2. PRISMA flowchart of study selection.

Oral Swabs in Adults

Fifteen studies (12 reports, 2,223 participants) evaluated oral swabs for adult TB diagnosis. Sensitivity ranged from 36% to 91%, and specificity from 66% to 100% (Figure 3). Tongue swabs (8 studies) showed higher sensitivity (52%–91%) compared to buccal swabs (36%–90%). The lowest sensitivity (52%) was reported in an asymptomatic screening cohort, while studies in symptomatic populations reported sensitivities of 66%–92%. Swab types included Whatman OmniSwab (30% of studies), Copan FLOQSwabs (25%), and others. PCR-based assays (14 studies) showed sensitivities of 36%–91%, whereas Xpert MTB/RIF Ultra (5 studies) demonstrated 45%–78% sensitivity with 100% specificity.

Figure 3. Forest plot (A) and SROC curve (B) for oral swab diagnostic accuracy in adults.

Oral Swabs in Children

Five studies (4 reports, 815 participants) assessed pediatric oral swabs. Sensitivity ranged from 8%–42% against microbiological reference standards and 5%–42% against composite standards, with specificity of 93%–100%. Heterogeneity in swab type, collection site, and NAAT methods precluded meta-analysis.

Figure 4. Forest plots for pediatric oral swabs using composite (A) and microbiological (B) reference standards.

Critical Analysis

Oral swab-based TB diagnosis offers significant public health potential, particularly for sputum-scarce populations. This review highlights moderate-to-high sensitivity in adults (36%–91%) but lower performance in children (5%–42%), likely due to paucibacillary disease and non-standardized reference criteria. Specificity remained consistently high (>90% in most studies). Key variables influencing accuracy include swab type (Copan FLOQSwabs outperformed others), sampling site (tongue swabs yielded stronger PCR signals), and NAAT choice (Xpert Ultra showed superior specificity).

Limitations: Heterogeneity in protocols (e.g., swab handling, storage) limited cross-study comparisons and meta-analysis. Many studies used lab-developed PCR assays, which may lack the reproducibility of commercial tests.

Future Directions: Standardized protocols for swab collection, processing, and analysis are urgently needed. Optimizing swab type, sampling techniques, and NAAT platforms could enhance sensitivity, particularly in children and paucibacillary cases.

Conclusion

Oral swab-based molecular testing demonstrates promising accuracy for TB diagnosis, with higher specificity than sensitivity. While adults show more consistent results, pediatric applications require further refinement. Standardization of protocols and validation in diverse populations will be critical for integrating oral swabs into global TB control strategies.

Click to View → Mantacc 93050L Oral Sampling Swabs

References

[1] Church EC, Steingart KR, Cangelosi GA, et al. Oral swabs with a rapid molecular diagnostic test for pulmonary tuberculosis in adults and children: a systematic review. Lancet Glob Health. 2024;12(1):e45-e54 . doi:10.1016/S2214-109X(23)00456-5.

Related Post

Oral Sampling Swabs: A Promising Alternative for Infectious Disease Diagnosis