Oral Swab Specimens Tested With Xpert MTB/RIF Ultra Assay for Diagnosis of Pulmonary Tuberculosis in Children: A Diagnostic Accuracy Study.

BACKGROUND: Microbiologic diagnosis of childhood tuberculosis may be difficult. Oral swab specimens are a potential noninvasive alternative to sputum specimens for diagnosis. METHODS: This was a prospective diagnostic accuracy study of oral swab specimens (buccal and tongue) for pulmonary tuberculosis diagnosis in children (aged ≤ 15 years) in 2 South African hospital sites. Children with cough of any duration as well as a positive tuberculin skin test result, tuberculosis contact, loss of weight, or chest radiograph suggestive of pulmonary tuberculosis were enrolled. Two induced sputum specimens were tested with Xpert MTB/RIF (or Xpert MTB/RIF Ultra) assay and liquid culture. Oral swab specimens were obtained before sputum specimens, frozen, and later tested with Xpert MTB/RIF Ultra. Children were classified as microbiologically confirmed tuberculosis, unconfirmed tuberculosis (receipt of tuberculosis treatment), or unlikely tuberculosis according to National Institutes of Health consensus definitions based on sputum microbiologic results. RESULTS: Among 291 participants (median age [interquartile range], 32 [14-73] months), 57 (20%) had human immunodeficiency virus (HIV), and 87 (30%) were malnourished; 90 (31%) had confirmed pulmonary tuberculosis (rifampicin resistant in 6 [7%] ), 157 (54%), unconfirmed pulmonary tuberculosis, and 44 (15%), unlikely tuberculosis. A single oral swab specimen was obtained from 126 (43%) of the participants (tongue in 96 and buccal in 30) and 2 swab specimens from 165 (57%) (tongue in 110 and buccal in 55). Sensitivity was low (22% [95% confidence interval, 15%-32%]) for all swab specimens combined (with confirmed pulmonary tuberculosis as reference), but specificity was high (100% [91%-100%]). The highest sensitivity was 33% (95% confidence interval, 15%-58%) among participants with HIV. The overall yield was 6.9% with 1 oral swab specimen and 7.2% with 2. CONCLUSIONS: Use of the Xpert MTB/RIF Ultra assay with oral swab specimens provides poor yield for microbiologic pulmonary tuberculosis confirmation in children.

Adrenal Vein Sampling in a Patient With Primary Hyperaldosteronism and Severe Contrast Allergy.

We report on a case of a 50-year-old female patient with primary hyperaldosteronism, in whom adrenal venous sampling was required to differentiate between unilateral and bilateral disease. Because of a history of severe allergy to iodinated contrast media, premedication with glucocorticoids was indicated. Exogenous glucocorticoids, however, can affect measurements of serum cortisol. To avoid this potential confounding effects on the cortisol assay, we decided to use dexamethasone instead of prednisolone or hydrocortisone. A high-dose adrenocorticotropin (ACTH) stimulation test with the simultaneous use of dexamethasone revealed an adequate adrenal cortisol response. ACTH-stimulated adrenal venous sampling showed reliable results, which provided a solid basis for further clinical decision-making.

The child ecosystem and childhood pulmonary tuberculosis: A South African perspective.

INTRODUCTION: This study investigates drivers of childhood pulmonary tuberculosis (PTB) using a childhood ecosystem approach in South Africa. An ecosystem approach toward identifying risk factors for PTB may identify targeted interventions. METHODS: Data were collected as part of a prospective cohort study of children presenting at a primary care facility or tertiary hospital with possible TB. Characterization of the childhood ecosystem included proximal, medial, and distal determinants. Proximal determinants included child characteristics that could impact PTB outcomes. Medial determinants included relational factors, such as caregiver health, which might impact interactions with the child. Distal determinants included macro-level determinants of disease, such as socioeconomic status and food insecurity. Children who started on TB treatment were followed for up to 6 months. Multivariate regression models tested independent associations between factors associated with PTB in children. RESULTS: Of 1202 children enrolled, 242 (20%) of children had confirmed PTB, 756 (63%) were started on TB treatment, and 444 (37%) had respiratory conditions other than TB. In univariate analyses, childhood malnutrition and caregiver smoking were associated with treated or confirmed PTB. In multivariate analyses, proximal factors, such as male gender and hospitalization, as well as low socioeconomic status as a distal factor, were associated with PTB. CONCLUSIONS: Interventions may need to target subgroups of children and families with elevated proximal, medial, and distal risk factors for PTB. Screening for risk factors, such as caregiver's health, may guide targeting. The provision of social protection programs to bolster economic security may be an important intervention for attenuating childhood exposure to risk factors.

Breath can discriminate tuberculosis from other lower respiratory illness in children.

Pediatric tuberculosis (TB) remains a global health crisis. Despite progress, pediatric patients remain difficult to diagnose, with approximately half of all childhood TB patients lacking bacterial confirmation. In this pilot study (n = 31), we identify a 4-compound breathprint and subsequent machine learning model that accurately classifies children with confirmed TB (n = 10) from children with another lower respiratory tract infection (LRTI) (n = 10) with a sensitivity of 80% and specificity of 100% observed across cross validation folds. Importantly, we demonstrate that the breathprint identified an additional nine of eleven patients who had unconfirmed clinical TB and whose symptoms improved while treated for TB. While more work is necessary to validate the utility of using patient breath to diagnose pediatric TB, it shows promise as a triage instrument or paired as part of an aggregate diagnostic scheme.

Accuracy of a Novel Urine Test, Fujifilm SILVAMP Tuberculosis Lipoarabinomannan, for the Diagnosis of Pulmonary Tuberculosis in Children.

BACKGROUND: An accurate point-of-care test for tuberculosis (TB) in children remains an elusive goal. Recent evaluation of a novel point-of-care urinary lipoarabinomannan test, Fujifilm SILVAMP Tuberculosis Lipoarabinomannan (FujiLAM), in adults living with human immunodeficiency virus (HIV) showed significantly superior sensitivity than the current Alere Determine Tuberculosis Lipoarabinomannan test (AlereLAM). We therefore compared the accuracy of FujiLAM and AlereLAM in children with suspected TB. METHODS: Children hospitalized with suspected TB in Cape Town, South Africa, were enrolled (consecutive admissions plus enrichment for a group of children living with HIV and with TB), their urine was collected and biobanked, and their sputum was tested with mycobacterial culture and Xpert MTB/RIF or Xpert MTB/RIF Ultra. Biobanked urine was subsequently batch tested with FujiLAM and AlereLAM. Children were categorized as having microbiologically confirmed TB, unconfirmed TB (clinically diagnosed), or unlikely TB. RESULTS: A total of 204 children were enrolled and had valid results from both index tests, as well as sputum microbiological testing. Compared to a microbiological reference standard, the sensitivity of FujiLAM and AlereLAM was similar (42% and 50%, respectively), but lower than that of Xpert MTB/RIF of sputum (74%). The sensitivity of FujiLAM was higher in children living with HIV (60%) and malnourished children (62%). The specificity of FujiLAM was substantially higher than that of AlereLAM (92% vs 66%, respectively). The specificity of both tests was higher in children 2 years or older (FujiLAM, 96%; AlereLAM, 72%). CONCLUSIONS: The high specificity of FujiLAM suggests utility as a "rule-in" test for children with a high pretest probability of TB, including hospitalized children living with HIV or with malnutrition.

Tuberculosis Diagnosis in Children Using Xpert Ultra on Different Respiratory Specimens.

Rationale: Microbiological confirmation of pulmonary tuberculosis in children is desirable.Objectives: To investigate the diagnostic accuracy and incremental yield of Xpert MTB/RIF Ultra (Ultra; Cepheid), a new rapid test, on repeated induced sputum, nasopharyngeal aspirates, and combinations of specimens.Methods: Consecutive South African children hospitalized with suspected pulmonary tuberculosis were enrolled.Measurements and Main Results: Induced sputum (IS) and nasopharyngeal aspirates (NPAs) were obtained. NPAs were frozen; IS underwent liquid culture, and an aliquot was frozen. Ultra was performed on thawed NPAs and IS specimens individually. Children were categorized as confirmed, unconfirmed, or unlikely tuberculosis according to NIH consensus case definitions. The diagnostic accuracy of Ultra was compared with liquid culture on IS. In total, 195 children (median age: 23.3 mo; 32 [16.4%] HIV-infected) had one IS and NPA, and 130 had two NPAs. There were 40 (20.5%) culture-confirmed cases. Ultra was positive on NPAs in 26 (13.3%) and on IS in 31 (15.9%). Sensitivity and specificity of Ultra on one NPA were 46% and 98%, respectively, and similar by HIV status. Sensitivity and specificity of Ultra on one IS were 74.3% and 96.9% respectively. Combining one NPA and one IS increased sensitivity to 80%. Sensitivity using Ultra on two NPAs was 54.2%, increasing to 87.5% with an IS Ultra.Conclusions: IS provides a better specimen than repeated NPA for rapid diagnosis using Ultra. However, Ultra testing of combinations of specimens provides a novel strategy that can be adapted to identify most children with confirmed pulmonary tuberculosis.

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

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.

Accuracy of Xpert Mtb/Rif Ultra for the Diagnosis of Pulmonary Tuberculosis in Children.

We determined the accuracy of the new Xpert MTB/RIF Ultra assay for diagnosis of pulmonary tuberculosis in children, using banked-induced sputum. Sensitivity and specificity were 75.3% and 96.9%, respectively, compared with a culture result from the same specimen. Of those children with microbiologically confirmed tuberculosis (positive Xpert, Ultra or culture), Xpert detected 63.2%, Ultra 73.7% and culture 82.9%.