Noninvasive Detection of Tuberculosis by Oral Swab Analysis

Abstract

Diagnostic tests for tuberculosis (TB) usually require collection of sputum, a viscous material derived from human airways. Sputum can be difficult and hazardous to collect and challenging to process in the laboratory. Oral swabs have been proposed as alternative sample types that are noninvasive and easy to collect. This study evaluated the biological feasibility of oral swab analysis (OSA) for the diagnosis of TB. Swabs were tested from South African adult subjects, including sputum GeneXpert MTB/RIF (GeneXpert)-confirmed TB patients (n = 138), sputum GeneXpert-negative but culture-positive TB patients (n = 10), ill non-TB patients (n = 37), and QuantiFERON-negative controls (n = 34). Swabs were analyzed by using a manual, nonnested quantitative PCR (qPCR) targeting IS6110. Two swab brands and three sites within the oral cavity were compared. Tongue swabbing yielded significantly stronger signals than cheek or gum swabbing. A flocked swab performed better than a more expensive paper swab. In a two-phase study, tongue swabs (two per subject) exhibited a combined sensitivity of 92.8% relative to sputum GeneXpert. Relative to all laboratory-diagnosed TB, the diagnostic yields of sputum GeneXpert (1 sample per subject) and OSA (2 samples per subject) were identical at 49/59 (83.1%) each. The specificity of the OSA was 91.5%. An analysis of “air swabs” suggested that most false-positive results were due to contamination of manual PCRs. With the development of appropriate automated methods, oral swabs could facilitate TB diagnosis in clinical settings and patient populations that are limited by the physical or logistical challenges of sputum collection.

Patient-collected tongue, nasal, and mid-turbinate swabs for SARS-CoV-2 yield equivalent sensitivity to health care worker collected nasopharyngeal swabs

“…Similarly, saliva collected from the tongue has also held promise. In a two-phase study, tongue swabs (two per subject) exhibited a combined sensitivity of 92.8% relative to sputum for tuberculosis detection in adults 12 , and exhibited promise as non-invasive samples for diagnosis of pediatric tuberculosis 13 .…”

Mycobacterium tuberculosis detection from oral swabs with Xpert MTB/RIF ULTRA: A pilot study

“…These results support the possible utility of oral swab samples for TB detection. Luabeya et al reported that Omniswab tongue swabs yielded significant better results compared to cheek swabs, with a sensitivity of 71.2% for a single swab and 83.1% for two swabs in 59 patients (case definition based on Xpert or liquid culture) and 83.1% for single swab in another group of 89 patients (compared to Xpert MTB/RIF) (2). Their additional use of sputum Xpert as the reference test and tongue swab may in part explain the higher observed sensitivity in their study and would be interesting adjustments to the Xpert protocol.…”

“…Participants were randomly assigned to one of three sample collection groups to assess collection methods and storage procedures: 1. Omniswab (Whatman, catalog #WB100035) in lysis buffer as described in (1,2); 2. Omniswab in phosphate buffered saline (PBS); 3.…”

Microbiological diagnosis of pulmonary tuberculosis in children by oral swab polymerase chain reaction

“…DNA was extracted from the swab samples by using a modified Qiagen protocol described previously 10,11 . Quantitative PCR targeting IS6110, a multi-copy insertion element unique to the M. tuberculosis complex, was done as described 11 . DNA extraction and qPCR were conducted in a 3-room laboratory suite with one-way workflow to minimize sample contamination.…”

“…One of the simplest samples to obtain is a swab of the oral mucosa 7 . Originally demonstrated for diagnosis of TB in non-human primates 8,9 , we have shown that oral swab PCR could detect approximately 90% of microbiologically confirmed cases of pulmonary TB in adults 10,11 . As potential samples for pulmonary TB testing in young children, oral swabs (OS) have the advantage of being universally obtainable with minimal discomfort or need for operator training.…”