Complementary non-sputum diagnostic testing using oral swabs and urine LAM testing for TB in people with HIV

Shapiro, Adrienne E.; Olson, Alaina M.; Kidoguchi, Lara; Niu, Xin; Ngcobo, Zinhele; Magcaba, Zanele P.; Ngwane, Mduduzi W.; Whitman, Grant R.; Weigel, Kris M.; Wood, Robin; Wilson, Doug; Drain, Paul K.; Cangelosi, Gerard A.

doi:10.1101/2022.02.16.22271079

Cited by 5 publications

(6 citation statements)

References 13 publications

(22 reference statements)

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“…Two more recent studies shed new light on potential strengths and limitations of the oral swab method. First, members of our consortium (17) reported a hybrid non-sputum strategy for people with HIV (PHIV), who often present with paucibacillary respiratory samples. When PHIV were tested for urine lipoarabinomannan (LAM) in addition to MTB DNA in oral swabs, the two samples yielded complementary results (urine LAM detected a lot of swabnegative people and vice versa).…”

Section: Discussionmentioning

confidence: 99%

“…When PHIV were tested for urine lipoarabinomannan (LAM) in addition to MTB DNA in oral swabs, the two samples yielded complementary results (urine LAM detected a lot of swabnegative people and vice versa). Testing both non-sputum specimens yielded significantly better sensitivity than testing either specimen alone (17). Secondly, Cox et al reported very low sensitivity (22%) for oral swabs collected from children with TB, when the swabs were tested with Xpert Ultra (18).…”

Section: Discussionmentioning

confidence: 99%

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Accuracy of Tongue Swab Testing Using Xpert MTB-RIF Ultra for Tuberculosis Diagnosis

et al. 2022

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Accuracy of Tongue Swab Testing Using Xpert MTB-RIF Ultra for Tuberculosis Diagnosis

et al. 2022

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“…Previous oral swab evaluations have used different types of sterile buffer matrices ranging from Tris-EDTA buffer (1,22), saline (11,23), sterile lysis buffer (50 mM Tris pH 8.0, 50 mM EDTA, 50 mM sucrose, 100 mM NaCl and 1% SDS) (12,24,25), or 7H9+OADC+Tween-80 (26) for storage or dry swab sample processing (1,2,11).…”

Section: Discussionmentioning

confidence: 99%

Optimal processing of tongue swab samples for Mycobacterium tuberculosis detection by the Xpert MTB/RIF Ultra assay

Chilambi,

Reiss,

Daivaa

et al. 2024

Preprint

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Tongue swabs represent a potential alternative to sputum as a sample type for detecting pulmonary tuberculosis (TB) using molecular diagnostic tests. The methods used to process tongue swabs for testing in the WHO-recommended Xpert MTB/RIF Ultra (Xpert Ultra) assay vary greatly. We aimed to identify the optimal method for processing diagnostic tongue swabs for subsequent testing by Xpert Ultra. We compared four methods for treating dry tongue swabs with Xpert Ultra sample reagent (SR) mixed with various concentrations of Tris-EDTA-Tween (TET), to treatment with SR alone or to a commonly used SR-free heat-inactivation protocol. In each condition, swabs obtained from volunteers without TB were placed into test buffer spiked with known amounts ofMycobacterium tuberculosis(Mtb) strain H37Rv-mc26230. Swabs processed with 1:1 diluted SR buffer had the lowestMtblimit of detection (LOD) at 22.7 CFU/700 µl (95% CI 14.2-31.2), followed by 2:1 diluted SR buffer at 30.3 CFU/700 µl (95% CI 19.9-40.7), neat SR at 30.9 CFU/700 µl (95% CI 21.5-40.3) and SR prefilled in the Xpert Ultra at 57.1 CFU/700 µl (95% CI 42.4-71.7). Swabs processed using the heat-based protocol had the highest LOD (77.6 CFU/700 µl; 95% CI 51.2–104.0). Similar findings were observed for LOD of RIF-susceptibility. Assay sensitivity using the 2:1 diluted SR buffer did not vary considerably in the presence of sputum matrix or phosphate buffer saline. Further studies are needed to assess the performance of this processing protocol in a clinical setting.ImportanceXpert MTB/RIF Ultra (Xpert Ultra) is approved by the World Health Organization for the diagnosis of tuberculosis (TB). This test is typically performed using sputum specimens obtained from people with presumptive TB. In order to inactivateMtband aid liquefaction, sputum must be mixed with Xpert SR prior to transfer into the Xpert Ultra. However, some people under evaluation for TB are unable to produce sputum. Alternative sample types for TB diagnosis would therefore be of value. Oral-swabs, including tongue-swabs have shown promise, but there are technical challenges associated with sample processing. In this study, several new tongue swab processing conditions were evaluated, utilizing SR, either neat or diluted in buffer. The ability of Xpert Ultra to detect TB was improved under these conditions compared with the previously published heat-processing method (1–3), processing steps were simplified, and technical challenges were overcome.

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“…We and others have shown that MTB DNA is deposited on the oral epithelium during active TB, and can be detected by oral swab analysis (OSA) [4][5][6][7][8][9][10][11][12][13][14][15]. In OSA, the dorsum of the tongue is brushed with a sterile swab.…”

Section: Introductionmentioning

confidence: 99%

Preferences of healthcare workers using tongue swabs for tuberculosis diagnosis during COVID-19

Codsi,

Errett,

Luabeya

et al. 2023

PLOS Glob Public Health

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Healthcare workers (HCWs) who come into contact with tuberculosis (TB) patients are at elevated risk of TB infection and disease. The collection and handling of sputum samples for TB diagnosis poses exposure risks to HCWs, particularly in settings where aerosol containment is limited. An alternative sample collection method, tongue swabbing, was designed to help mitigate this risk, and is under evaluation in multiple settings. This study assessed risk perceptions among South African HCWs who used tongue swabbing in TB diagnostic research during the COVID-19 pandemic. We characterized their context-specific preferences as well as the facilitators and barriers of tongue swab use in clinical and community settings. Participants (n = 18) were HCWs with experience using experimental tongue swabbing methods at the South African Tuberculosis Vaccine Initiative (SATVI). We used key informant semi-structured interviews to assess attitudes toward two tongue swab strategies: Provider-collected swabbing (PS) and supervised self-swabbing (SSS). Responses from these interviews were analyzed by rapid qualitative analysis and thematic analysis methods. Facilitators included aversion to sputum (PS and SSS), perceived safety of the method (SSS), and educational resources to train patients (SSS). Barriers included cultural stigmas, as well as personal security and control of their work environment when collecting swabs in community settings. COVID-19 risk perception was a significant barrier to the PS method. Motivators for HCW use of tongue swabbing differed substantially by use case, and whether the HCW has the authority and agency to implement safety precautions in specific settings. These findings point to a need for contextually specific educational resources to enhance safety of and adherence to the SSS collection method.

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Complementary non-sputum diagnostic testing using oral swabs and urine LAM testing for TB in people with HIV

Cited by 5 publications

References 13 publications

Accuracy of Tongue Swab Testing Using Xpert MTB-RIF Ultra for Tuberculosis Diagnosis

Accuracy of Tongue Swab Testing Using Xpert MTB-RIF Ultra for Tuberculosis Diagnosis

Optimal processing of tongue swab samples for Mycobacterium tuberculosis detection by the Xpert MTB/RIF Ultra assay

Preferences of healthcare workers using tongue swabs for tuberculosis diagnosis during COVID-19

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