Culture is an imperfect and heterogeneous reference standard in pediatric tuberculosis

DiNardo, Andrew; Detjen, Anne; Ustero, Pilar; Ngo, Katherine; Bacha, Jason; Mandalakas, Anna M.

doi:10.1016/j.tube.2016.09.021

Cited by 40 publications

(24 citation statements)

References 7 publications

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“…For example, the Xpert MTB/RIF assay (Xpert; Cepheid, Sunnydale, CA) has 62 to 66% sensitivity compared to culture for the diagnosis of pediatric PTB ( 2 ), and 68% for smear-negative PTB in adults ( 3 ). However, even culture in these patient groups confirms <50% of cases ( 4 – 6 ), partly due to low bacterial burden and the difficulty in obtaining high-quality sputum specimens ( 6 , 7 ).…”

Section: Introductionmentioning

confidence: 90%

Stool Culture for Diagnosis of Pulmonary Tuberculosis in Children

et al. 2017

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Bacteriological confirmation of Mycobacterium tuberculosis 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 (N-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 M. tuberculosis. 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 M. tuberculosis detection in children with intrathoracic TB. Reducing culture contamination through improved laboratory protocols may enable more reliable estimates of its diagnostic utility.

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Section: Introductionmentioning

confidence: 90%

Stool Culture for Diagnosis of Pulmonary Tuberculosis in Children

et al. 2017

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“…Sputum induction and gastric aspiration can be used to obtain respiratory specimens from children unable to expectorate sputum; however, gastric aspiration is invasive and neither procedure is widely implemented in resource-constrained settings. Due to these diagnostic challenges, bacteriologic confirmation of TB is obtained in only a small minority of children diagnosed with TB [2–4].…”

Section: Introductionmentioning

confidence: 99%

Detection of Mycobacterium tuberculosis in pediatric stool samples using TruTip technology

et al. 2019

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Background Rapid and accurate diagnosis of childhood tuberculosis (TB) is challenging because children are often unable to produce the sputum sample required for conventional tests. Stool is an alternative sample type that is easy to collect from children, and studies investigating the use of stool for molecular detection of Mycobacterium tuberculosis (Mtb) have led to promising results. Our objective was to evaluate stool as an alternative specimen to sputum for Mtb detection in children. We did so using the TruTip workstation (Akonni Biosystems), a novel automated lysis and extraction platform. Methods We tested stool samples from 259 children aged 0–14 years old, in Lima, Peru who presented with TB symptoms. Following extraction with TruTip, we detected the presence of Mtb DNA by IS6110 real-time PCR. We calculated assay sensitivity in two groups: (1) children with culture confirmed TB ( N = 22); and (2) children with clinically-diagnosed unconfirmed TB ( N = 84). We calculated specificity among children in whom TB was ruled out ( N = 153). Among children who were diagnosed with TB, we examined factors associated with a positive stool test. Results Assay sensitivity was 59% (95% confidence interval [CI]: 39–80%) and 1.2% (95% CI: 0.0–6.5%) in children with culture-confirmed and clinically-diagnosed unconfirmed TB, respectively, and specificity was 97% (95% CI: 93–99%). The assay detected Mtb in stool of 7/7 children with smear-positive TB (100% sensitivity; 95% CI: 59–100%), and in 6/15 of children with smear-negative, culture-confirmed TB (40% sensitivity; 95% CI: 16–68%). Older age, smear positivity, culture positivity, ability to produce sputum and cavitary disease were associated with a positive stool result. Conclusion Testing of stool samples with the TruTip workstation and IS6110 amplification yielded sensitivity and specificity estimates comparable to other tests such as Xpert. Future work should include detection of resistance using the TruTip closed amplification system and assay optimization to improve sensitivity in children with low bacillary loads.

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“…[12][13][14][15] Microbiological testing for child TB is complicated by barriers to specimen collection and poor sensitivity in detecting paucibacillary disease, so child TB cases in high-burden areas are predominately diagnosed via clinical determination. 16,17 Herein, we describe factors associated with active child TB among child contacts evaluated as part of our community-based contact-tracing project, BUTIMBA.…”

Section: Introductionmentioning

confidence: 99%

Distinct Risk Factors for Clinical and Bacteriologically Confirmed Tuberculosis among Child Household Contacts in a High-Burden Setting

Sandoval

Swamy

Kay³

et al. 2020

The American Journal of Tropical Medicine and Hygiene

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The identification and screening of children at high risk of tuberculosis is essential to the control and prevention of child tuberculosis (TB). BUTIMBA, an active case finding and household contact-tracing project implemented between 2013 and 2015 in Eswatini, evaluated 5,413 contacts of 1,568 index cases, of whom 82 (1.5%) were diagnosed with TB disease. We conducted univariate and multivariate clustered logistic regression analyses of risk factors for any TB diagnosis among child household contacts of TB cases. Children younger than 5 years and children with positive HIV status were more likely to have TB than children aged 5-14 years and children with negative HIV status, respectively (adjusted odds ratio [aOR]: 2.2, P < 0.001; aOR: 5.0, P < 0.001). Children with one or more TB symptoms were more likely to be diagnosed with TB based on clinical criteria, but less likely to have bacteriologically confirmed TB, highlighting subjectivity in determination of child TB.

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Culture is an imperfect and heterogeneous reference standard in pediatric tuberculosis

Cited by 40 publications

References 7 publications

Stool Culture for Diagnosis of Pulmonary Tuberculosis in Children

Stool Culture for Diagnosis of Pulmonary Tuberculosis in Children

Detection of Mycobacterium tuberculosis in pediatric stool samples using TruTip technology

Distinct Risk Factors for Clinical and Bacteriologically Confirmed Tuberculosis among Child Household Contacts in a High-Burden Setting

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