Background Tuberculosis (TB) continues to result in high morbidity and mortality in children from resource-limited settings. Diagnostic challenges, including resource-intense sputum collection methods and insensitive diagnostic tests, contribute to diagnostic delay and poor outcomes in children. We evaluated the diagnostic utility of stool Xpert MTB/RIF (Xpert) compared with bacteriologic confirmation (combination of Xpert and culture of respiratory samples). Methods In a hospital-based study in Cape Town, South Africa, we enrolled children younger than 13 years of age with suspected pulmonary TB from April 2012- August 2015. Standard clinical investigations included tuberculin skin test, chest radiograph and HIV testing. Respiratory samples for smear microscopy, Xpert and liquid culture included gastric aspirates, induced sputum, nasopharyngeal aspirates and expectorated sputum. One stool sample per child was collected and tested using Xpert. Results Of 379 children enrolled (median age, 15.9 months, 13.7% HIV-infected), 73 (19.3%) had bacteriologically confirmed TB. The sensitivity and specificity of stool Xpert vs. overall bacteriologic confirmation were 31.9% (95% CI 21.84-44.50%) and 99.7% (95% CI 98.2-100%) respectively. 23/51 (45.1%) children with bacteriologically confirmed TB with severe disease were stool Xpert positive. Cavities on chest radiograph were associated with Xpert stool positivity regardless of age and other relevant factors (OR 7.05; 95% CI 2.16-22.98; p=0.001). Conclusions Stool Xpert can rapidly confirm TB in children who present with radiologic findings suggestive of severe TB. In resource-limited settings where children frequently present with advanced disease, Xpert on stool samples could improve access to rapid diagnostic confirmation and appropriate treatment.

BAL Xpert resulted in additional diagnostic yield and also in the rapid detection of drug resistance in children with complicated intrathoracic TB. The clinical impact of this modality should be further evaluated in children.

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.

The microbiological diagnosis of tuberculosis (TB) in children is challenging, as it relies on the collection of relatively invasive specimens by trained health care workers, which is not feasible in many settings. Mycobacterium tuberculosis is detectable from the stools of children using molecular methods, but processing stool specimens is resource intensive.

Three-hundred four young children with suspected pulmonary tuberculosis had a gastric aspirate, induced sputum and nasopharyngeal aspirate collected on each of 2 consecutive weekdays. Specimens collected on the second day were pooled in the laboratory for each child individually. The diagnostic yield by Xpert and culture from pooled specimens was not significantly different to a single gastric aspirate.

Introduction: Bronchoscopy can be a useful tool in children with pulmonary tuberculosis (PTB) with severe disease potentially requiring intervention or in the face of diagnostic dilemmas. The aim of this study was to determine the value of Xpert MTB/RIF assay (Xpert) on bronchoalveolar lavage (BAL) samples in children with complicated PTB. Methods: Retrospective analysis of children with clinically diagnosed PTB, who underwent routine bronchoscopy over a 5-year period at a large referral hospital. BAL and other respiratory samples were tested by microscopy, culture, and Xpert. We explored whether clinical, radiographic and bronchoscopy findings, and duration of antituberculosis treatment were associated with bacteriological confirmation. Results: One hundred and twelve out of one hundred and forty-six (76.7%) children (median age 16 months) were on antituberculosis treatment for a median of 10 days at the time of bronchoscopy. Overall, bacteriological confirmation was achieved in 115 (78.7%), with 101 (69.2%) detected on BAL. Of those bacteriologically confirmed on BAL, 61.4% were positive by both Xpert and culture, 34.7% only by Xpert, and 3.9% only by culture. Sensitivity and specificity of Xpert compared with culture on BAL samples for children not on antituberculosis treatment were 94.1% (95% confidence interval [CI]: 71.3, 99.8) and 68.7% (95% CI: 41.3, 89.0), respectively. Conclusions: In children undergoing bronchoscopy for complicated PTB, Xpert testing of BAL had a high diagnostic yield in children already on antituberculosis treatment. Bronchoscopy should be considered if noninvasive respiratory specimens fail to confirm complicated TB.

Background: We determined mycobacterial drug resistance and HIV prevalence among children with bacteriologically confirmed tuberculosis (TB) from March 2013 to February 2017. Results were compared with 5 previous 2-year surveillance studies (2003–2013). Methods: Prospective surveillance of all bacteriologically confirmed TB in children (0–13 years) completed at Tygerberg Hospital, Cape Town, South Africa. Drug susceptibility testing was done by GenoType MTBDRplus for isoniazid and rifampicin; ofloxacin and amikacin drug susceptibility testing was completed if rifampicin resistance was detected. Xpert MTB/RIF was routinely introduced during this period. Results: Six hundred sixty-two children, median age 34 months (interquartile range 14–79) had bacteriologically confirmed TB; 587 (88.7%) were culture-confirmed and 75 (11.3%) confirmed by Xpert MTB/RIF only. Of culture-confirmed cases, 509 (86.7%) were pan-susceptible, 47 (8.0%) were multidrug-resistant, 13 (2.2%) were RIF-resistant/INH-susceptible and 18 (3.1%) were INH-resistant/RIF-susceptible. Of Xpert-positive cases, 3/75 (4%), 68/75 (92%) and 4/75 (5%) were RIF-resistant, RIF-susceptible and RIF-indeterminate, respectively. Of 573 (97.6%) children tested, 74 (12.9%) were HIV positive. Compared with previous surveillance periods, RIF mono-resistance increased from 0% to 2.2% (trend test: χ2 = 7.050, P = 0.0079). HIV prevalence decreased from 29% to 10.6% (trend test: χ2 = 27.975, P < 0.0001). Of multidrug-resistant cases, 15/47 (32%) were ofloxacin resistant. Conclusions: The increase in RIF-resistant/INH-susceptible cases and ofloxacin resistance among multidrug-resistant TB cases in children, indicative of recent transmission, is concerning. The prevalence of multidrug-resistant TB remains high in children.

Background Despite a high paediatric tuberculosis (TB) burden globally, sensitive and specific diagnostic tools are lacking. In addition, no data exist on the impact of pulmonary TB on long-term child lung health in low- and middle-income countries. The prospective observational UMOYA study aims (1) to build a state-of-the-art clinical, radiological, and biological repository of well-characterised children with presumptive pulmonary TB as a platform for future studies to explore new emerging diagnostic tools and biomarkers for early diagnosis and treatment response; and (2) to investigate the short and long-term impact of pulmonary TB on lung health and quality of life in children. Methods We will recruit up to 600 children (0–13 years) with presumptive pulmonary TB and 100 healthy controls. Recruitment started in November 2017 and is expected to continue until May 2023. Sputum and non-sputum-based samples are collected at enrolment and during follow-up in TB cases and symptomatic controls. TB treatment is started by routine care services. Intensive follow-up for 6 months will allow for TB cases to retrospectively be classified according to international consensus clinical case definitions for TB. Long-term follow-up, including imaging, comprehensive assessment of lung function and quality of life questionnaires, are done yearly up to 4 years after recruitment. Discussion The UMOYA study will provide a unique platform to evaluate new emerging diagnostic tools and biomarkers for early diagnosis and treatment response and to investigate long-term outcomes of pulmonary TB and other respiratory events on lung health in children.