Childhood pulmonary TB (PTB) is under diagnosed, in part due to difficulties in obtaining microbiological confirmation. However, given the poor specificity of clinical diagnosis, microbiological confirmation and drug susceptibility testing is important in guiding appropriate therapy especially in the context of drug resistant TB. Confirmation is often possible, even in infants and young children, if adequate specimens are collected. Culture yield varies with the severity of illness, specimen type and culture method. Induced sputum is recognised as a safe procedure with a high diagnostic yield. Advances include optimised protocols for smear microscopy and modified culture techniques, such as the Microscopic Observation Drug Susceptibility Assay. Detection of Mycobacterium tuberculosis nucleic acid in respiratory specimens has high specificity but relatively poor sensitivity, particularly for smear negative disease. The recent development of an integrated specimen processing and real-time PCR testing platform for M. tuberculosis and rifampicin resistance is an important advance that requires evaluation in childhood TB.2010 Elsevier Ltd. All rights reserved.

Bacteriological confirmation of is achieved in the minority of young children with tuberculosis (TB), since specimen collection is resource intensive and respiratory secretions are mostly paucibacillary, leading to limited sensitivity of available diagnostic tests. Although molecular tests are increasingly available globally, mycobacterial culture remains the gold standard for diagnosis and determination of drug susceptibility and is more sensitive than molecular methods for paucibacillary TB. We evaluated stool culture as an alternative to respiratory specimens for the diagnosis of suspected intrathoracic TB in a subgroup of 188 children (median age, 14.4 months; 15.4% HIV infected) enrolled in a TB diagnostic study at two local hospitals in Cape Town, South Africa. One stool culture was compared to overall bacteriological confirmation by stool Xpert and by Xpert and culture of multiple respiratory specimens. After decontamination/digestion with NALC (-acetyl-l-cysteine)-NaOH (1.25%), concentrated fluorescent smear microscopy, Xpert MTB/RIF, and liquid culture were completed for all specimens. Culture contamination of stool specimens was high at 41.5%. Seven of 90 (7.8%) children initiating TB treatment were stool culture positive for Excluding contaminated cultures, the sensitivity of stool culture versus confirmed TB was 6/25 (24.0%; 95% confidence interval [CI] = 9.4 to 45.1%). In addition, stool culture detected TB in 1/93 (1.1%) children with "unconfirmed TB." Testing the same stool by Xpert increased sensitivity to 33.3% (95% CI = 18.0 to 51.8%). In conclusion, stool culture had low sensitivity for detection in children with intrathoracic TB. Reducing culture contamination through improved laboratory protocols may enable more reliable estimates of its diagnostic utility.Copyright © 2017 Walters et al.

Self-collected specimens have been advocated to avoid infectious exposure to healthcare workers. Self-induced sputum in those with a productive cough and saliva in those without a productive cough have been proposed, but sensitivity remains uncertain.We performed a prospective study in 2 regional hospitals in Hong Kong.We prospectively examined 563 serial samples collected during the virus shedding periods of 50 patients: 150 deep throat saliva (DTS), 309 pooled-nasopharyngeal (NP) and throat swabs, and 104 sputum. Deep throat saliva had the lowest overall reverse-transcriptase polymerase chain reaction (RT-PCR)-positive rate (68.7% vs 89.4% [sputum] and 80.9% [pooled NP and throat swabs]) and the lowest viral ribonucleic acid (RNA) concentration (mean log copy/mL 3.54 vs 5.03 [sputum] and 4.63 [pooled NP and throat swabs]). Analyses with respect to time from symptom onset and severity also revealed similar results. Virus yields of DTS correlated with that of sputum (Pearson correlation index 0.76; 95% confidence interval, 0.62-0.86). We estimated that the overall false-negative rate of DTS could be as high as 31.3% and increased 2.7 times among patients without sputum.Deep throat saliva produced the lowest viral RNA concentration and RT-PCR-positive rate compared with conventional respiratory specimens in all phases of illness. Self-collected sputum should be the choice for patients with sputum.© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

The value of the "trace" result in Xpert Ultra for diagnosing active tuberculosis (TB) remains unclear. Our study evaluated the diagnostic accuracy of Xpert MTB/RIF Ultra (Xpert Ultra) (Cepheid, Sunnyvale, USA) over Xpert MTB/RIF (Xpert) (Cepheid, Sunnyvale, USA) and mycobacterial culture when compared with a composite reference standard (CRS).A retrospective single-center observational study was conducted in a tertiary care hospital in South India. Over three months, patients (aged ≥15 years) data on Xpert Ultra tests and mycobacterial culture of pulmonary and extrapulmonary samples were extracted from their electronic medical records. Patients were defined as TB cases based on the CRS criteria. Sensitivity, specificity, positive and negative predictive values of diagnostic tests were calculated by comparing them to the CRS.Xpert Ultra was more sensitive (87.8%) than Xpert (72.1%) and culture (44.1%). The specificity of Xpert Ultra was lower (98.1%) than those of Xpert (100%) and culture (100%). The sensitivity (92%) and specificity (100%) of Xpert Ultra were highest when performed on pus samples.Xpert Ultra with the trace category is superior to the conventional Xpert, and mycobacterial culture in identifying TB.Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Diagnosis of pulmonary tuberculosis (TB) usually includes laboratory analysis of sputum, a viscous material derived from deep in the airways of patients with active disease. As a diagnostic sample matrix, sputum can be difficult to collect and analyze by microbiological and molecular techniques. An alternative, less invasive sample matrix could greatly simplify TB diagnosis. We hypothesized that Mycobacterium tuberculosis cells or DNA accumulate on the oral epithelia of pulmonary TB patients and can be collected and detected by using oral (buccal) swabs. To test this hypothesis, 3 swabs each were collected from 20 subjects with active pulmonary TB and from 20 healthy controls. Samples were tested by using a polymerase chain reaction (PCR) specific to the M. tuberculosis IS6110 insertion element. Eighteen out of 20 confirmed case subjects (90%) yielded at least 2 positive swabs. Healthy control samples were 100% negative. This case-control study supports past reports of M. tuberculosis DNA detection in oral swabs. Oral swab samples are non-invasive, non-viscous and easy to collect with or without active TB symptoms. These characteristics may enable simpler and more active TB case finding strategies.

Microbiological diagnosis of pediatric pulmonary tuberculosis (TB) is challenging due to the difficulty of collecting and testing sputum from children. We investigated whether easily-obtained oral swab samples are useful alternatives or supplements to sputum. Oral swabs and induced sputum (IS) were collected from 201 South African children with suspected pulmonary TB. IS samples were tested by mycobacterial culture and Xpert MTB/RIF. Oral swabs were tested by PCR targeting IS6110. Children were categorized as Confirmed TB (microbiologic confirmation on IS), Unconfirmed TB (clinical diagnosis only), or Unlikely TB (recovery without TB treatment). Relative to Confirmed TB, PCR on two oral swabs per child was 43% sensitive and 93% specific. This sensitivity fell below that of sputum Xpert (64%). Among children with either Confirmed or Unconfirmed TB, PCR on two oral swabs per child was 31% sensitive and 93% specific, which was more sensitive than sputum testing among this group (21%). Although oral swab analysis had low sensitivity in sputum-positive children, it detected TB in a significant proportion of sputum-negative children who were clinically diagnosed with TB. Specificity at 93% was suboptimal but may improve with the use of automated methods. With further development, oral swabs may become useful supplements to sputum as samples for diagnosis of pulmonary TB in children.

We evaluated diagnostic performance of oral swab analysis (OSA) for tuberculosis (TB) in a high HIV/TB burden setting in Kenya.