Xpert-Ultra Assay in Stool and Urine Samples to Improve Tuberculosis Diagnosis in Children: The Médecins Sans Frontières Experience in Guinea-Bissau and South Sudan.

Background: More than half of childhood tuberculosis cases remain undiagnosed yearly. The World Health Organization recommends the Xpert-Ultra assay as a first pediatric diagnosis test, but microbiological confirmation remains low. We aimed to determine the diagnostic performance of Xpert-Ultra with stool and urine samples in presumptive pediatric tuberculosis cases in 2 high-tuberculosis-burden settings. Methods: This Médecins Sans Frontières cross-sectional multicentric study took place at Simão Mendes Hospital, Guinea-Bissau (July 2019 to April 2020) and in Malakal Hospital, South Sudan (April 2021 to June 2023). Children aged 6 months to 15 years with presumptive tuberculosis underwent clinical and laboratory assessment, with 1 respiratory and/or extrapulmonary sample (reference standard [RS]), 1 stool, and 1 urine specimen analyzed with Xpert-Ultra. Results: A total of 563 children were enrolled in the study, 133 from Bissau and 400 from Malakal; 30 were excluded. Confirmation of tuberculosis was achieved in 75 (14.1%), while 248 (46.5%) had unconfirmed tuberculosis. Of 553 with an RS specimen, the overall diagnostic yield was 12.4% (66 of 533). A total of 493 stool and 524 urine samples were used to evaluate the performance of Xpert-Ultra with these samples. Compared with the RS, the sensitivity and specificity of Xpert-Ultra were 62.5% (95% confidence interval, 49.4%-74%) and 98.3% (96.7%-99.2%), respectively, with stool samples, and 13.9% (7.5%-24.3%) and 99.4% (98.1%-99.8%) with urine samples. Nine patients were positive with stool and/or urine samples but negative with the RS. Conclusions: Xpert-Ultra in stool samples showed moderate to high sensitivity and high specificity compared with the RS and an added diagnostic yield when RS results were negative. Xpert-Ultra in stool samples was useful in extrapulmonary cases. Xpert-Ultra in urine samples showed low test performance. Clinical Trials Registration: NCT06239337.

Point-of-care ultrasound for tuberculosis diagnosis in children: a Médecins Sans Frontières cross-sectional study in Guinea-Bissau.

OBJECTIVE: Description of tuberculosis (TB)-focused point-of-care ultrasound (POCUS) findings for children with presumptive TB. DESIGN: Cross-sectional study (July 2019 to April 2020). SETTING: Simão Mendes hospital in Bissau, a setting with high TB, HIV, and malnutrition burdens. PARTICIPANTS: Patients aged between 6 months and 15 years with presumptive TB. INTERVENTIONS: Participants underwent clinical, laboratory and unblinded clinician-performed POCUS assessments, to assess subpleural nodules (SUNs), lung consolidation, pleural and pericardial effusion, abdominal lymphadenopathy, focal splenic and hepatic lesions and ascites. Presence of any sign prompted a POCUS positive result. Ultrasound images and clips were evaluated by expert reviewers and, in case of discordance, by a second reviewer. Children were categorised as confirmed TB (microbiological diagnosis), unconfirmed TB (clinical diagnosis) or unlikely TB. Ultrasound findings were analysed per TB category and risk factor: HIV co-infection, malnutrition and age. RESULTS: A total of 139 children were enrolled, with 62 (45%) women and 55 (40%) aged <5 years; 83 (60%) and 59 (42%) were severely malnourished (SAM) and HIV-infected, respectively. TB confirmation occurred in 27 (19%); 62 (45%) had unconfirmed TB and 50 (36%) had unlikely TB. Children with TB were more likely to have POCUS-positive results (93%) compared with children with unlikely TB (34%). Common POCUS signs in patients with TB were: lung consolidation (57%), SUNs (55%) and pleural effusion (30%), and focal splenic lesions (28%). In children with confirmed TB, POCUS sensitivity was 85% (95% CI) (67.5% to 94.1%). In those with unlikely TB, specificity was 66% (95% CI 52.2% to 77.6%). Unlike HIV infection and age, SAM was associated with a higher POCUS-positivity. Cohen's kappa coefficient for concordance between field and expert reviewers ranged from 0.6 to 0.9. CONCLUSIONS: We found a high prevalence of POCUS signs in children with TB compared with children with unlikely TB. POCUS-positivity was dependent on nutritional status but not on HIV status or age. TB-focused POCUS could potentially play a supportive role in the diagnosis of TB in children. TRIAL REGISTRATION NUMBER: NCT05364593.

Post-tuberculosis sequelae in children and adolescents: a systematic review.

In 2020, an estimated total of 155 million people had survived tuberculosis. Among this number, a sizable proportion have considerable post-tuberculosis morbidity, as shown for the adult population. This systematic review aims to identify the spectrum and prevalence of post-tuberculosis sequelae in children and adolescents. Four databases were systematically searched from database inception to Feb 7, 2022, for literature on post-treatment outcomes of tuberculosis acquired during childhood. Of the 4613 identified publications, 71 studies were included in this systematic review. Studies on cohorts with comparably rare (most of which were extrapulmonary) tuberculosis presentations, such as spinal tuberculosis and tuberculous meningitis were over-represented; however, no study assessed long-term sequelae in a cohort with an average childhood tuberculosis spectrum. The descriptive analysis includes long-term outcomes of 3529 paediatric patients 1 month to 36 years after confirmed (47%) or clinical (53%) tuberculosis. In a considerable proportion of children, a broad spectrum of post-tuberculosis sequelae were identified, ranging from radiological residua after pulmonary tuberculosis, to disabling deformities after musculoskeletal and cutaneous tuberculosis, to somatic and psychosocial impairment after tuberculous meningitis. A better understanding and comprehensive assessment of post-tuberculosis sequelae in children are needed to improve tuberculosis care beyond antituberculous treatment.

Task shifting for point of care ultrasound in primary healthcare in low- and middle-income countries-a systematic review.

Low-and middle-income countries (LMIC) are faced with healthcare challenges including lack of specialized healthcare workforce and limited diagnostic infrastructure. Task shifting for point-of-care ultrasound (POCUS) can overcome both shortcomings. This review aimed at identifying benefits and challenges of task shifting for POCUS in primary healthcare settings in LMIC. Medline and Embase were searched up to November 22nd, 2021. Publications reporting original data on POCUS performed by local ultrasound naïve healthcare providers in any medical field at primary healthcare were included. Data were analyzed descriptively. PROSPERO registration number CRD42021223302. Overall, 36 publications were included, most (n = 35) were prospective observational studies. Medical fields of POCUS application included obstetrics, gynecology, emergency medicine, infectious diseases, and cardiac, abdominal, and pulmonary conditions. POCUS was performed by midwives, nurses, clinical officers, physicians, technicians, and community health workers following varying periods of short-term training and using different ultrasound devices. Benefits of POCUS were yields of diagnostic images with adequate interpretation impacting patient management and outcome. High cost of face-to-face training, poor internet connectivity hindering telemedicine components, and unstable electrici'ty were among reported drawbacks for successful implementation of task shifting POCUS. At the primary care level in resource-limited settings task shifting for POCUS has the potential to expand diagnostic imaging capacity and impact patient management leading to meaningful health outcomes.

Transthoracic mediastinal ultrasound in childhood tuberculosis: A review.

Diagnosing childhood tuberculosis (TB) is challenging, and novel diagnostic tools are urgently needed. Mediastinal lymphadenopathy is a hallmark of primary pulmonary TB (PTB) in children. We aimed to summarise available methodological and diagnostic data of transthoracic mediastinal ultrasound for childhood TB. Literature review identified two prospective and three retrospective studies, a case report, and a technical report including cases. All reported on suprasternal scanning of the mediastinum; additional parasternal scanning was reported by five studies. The proportion of children with lymphadenopathy detected by mediastinal ultrasound ranged between 15% and 85%, with studies including both supra- and parasternal scanning achieving higher detection ratios. Three retrospective studies reported mediastinal lymphadenopathy on ultrasound for most cases presenting with a normal or inconclusive CXR. Data on ultrasound for mediastinal lymphadenopathy in children are limited but indicate that mediastinal ultrasound can successfully detect mediastinal lymphadenopathy in children with TB.

Pulmonary aspergilloma on transthoracic ultrasound.

PURPOSE: Pulmonary aspergilloma affects immunocompromised patients but is also a recurrent condition in patients previously treated for pulmonary tuberculosis. METHODS AND RESULTS: We report the case of a 45-year-old patient with a history of cured pulmonary tuberculosis 15 years earlier in whom we visualized pulmonary aspergilloma by transthoracic lung sonography. Sonography of pulmonary aspergilloma demonstrated an oval cavity with hypoechoic contents and an irregular border, measuring a diameter of 4.7 cm; inside the lesion, a roundish structure with an anechoic rim was discernable. CONCLUSIONS: The sonographic findings corresponded to chest X-ray and computed tomography imaging in this patient and to previously reported sonographic characteristics of mycotic abscesses in other organs. Lung ultrasound may be a tool to identify pulmonary aspergilloma, especially as a point-of-care imaging tool and where other imaging modalities are inaccessible.