BACKGROUND: Diagnosis of tuberculosis should be improved in children infected with HIV to reduce mortality. We developed prediction scores to guide antituberculosis treatment decision in HIV-infected children with suspected tuberculosis. METHODS: HIV-infected children with suspected tuberculosis enrolled in Burkina Faso, Cambodia, Cameroon, and Vietnam (ANRS 12229 PAANTHER 01 Study), underwent clinical assessment, chest radiography, Quantiferon Gold In-Tube (QFT), abdominal ultrasonography, and sample collection for microbiology, including Xpert MTB/RIF (Xpert). We developed 4 tuberculosis diagnostic models using logistic regression: (1) all predictors included, (2) QFT excluded, (3) ultrasonography excluded, and (4) QFT and ultrasonography excluded. We internally validated the models using resampling. We built a score on the basis of the model with the best area under the receiver operating characteristic curve and parsimony. RESULTS: A total of 438 children were enrolled in the study; 251 (57.3%) had tuberculosis, including 55 (12.6%) with culture- or Xpert-confirmed tuberculosis. The final 4 models included Xpert, fever lasting >2 weeks, unremitting cough, hemoptysis and weight loss in the past 4 weeks, contact with a patient with smear-positive tuberculosis, tachycardia, miliary tuberculosis, alveolar opacities, and lymph nodes on the chest radiograph, together with abdominal lymph nodes on the ultrasound and QFT results. The areas under the receiver operating characteristic curves were 0.866, 0.861, 0.850, and 0.846, for models 1, 2, 3, and 4, respectively. The score developed on model 2 had a sensitivity of 88.6% and a specificity of 61.2% for a tuberculosis diagnosis. CONCLUSIONS: Our score had a good diagnostic performance. Used in an algorithm, it should enable prompt treatment decision in children with suspected tuberculosis and a high mortality risk, thus contributing to significant public health benefits.

There is no microbiological gold standard for childhood tuberculosis (TB) diagnosis. The paucibacillary nature of the disease, challenges in sample collection in young children, and the limitations of currently available microbiological tests restrict microbiological confirmation of intrathoracic TB to the minority of children. Recent WHO guidelines recommend the use of novel rapid molecular assays as initial diagnostic tests for TB and endorse alternative sample collection methods for children. However, the uptake of these tools in high-endemic settings remains low. In this review, we appraise historic and new microbiological tests and sample collection techniques that can be used for the diagnosis of intrathoracic TB in children. We explore challenges and possible ways to improve diagnostic yield despite limitations, and identify research gaps to address in order to improve the microbiological diagnosis of intrathoracic TB in children.

There has been a global pursuit to improve the diagnosis of tuberculosis in young children by applying diagnostic methods on accessible biospecimens such as stool. We aimed to conduct a systematic review on the accuracy of stool-based molecular tests for tuberculosis diagnosis in children and to assess the impact of the available pre-processing methods and other design characteristics. In this systematic review and meta-analysis, we evaluated studies in children younger than 16 years with presumptive tuberculosis that were published in English, Spanish, French, and Portuguese from Jan 1, 2000, to May 3, 2024, in MEDLINE, Embase, and Embase Classic, comparing the molecular detection of Mycobacterium tuberculosis DNA in stool with microbiological tests on other samples or a clinical diagnosis. We did not exclude studies based on geographical location, sample size, or study design if they were reporting primary data. Two independent reviewers (LC-C and SM) screened titles, abstracts, and full-text articles for eligibility and extracted data on study characteristics, study population, and diagnostic performance. If information relevant to the main analysis was not reported in the article, the corresponding authors were contacted. Point estimates and 95% CIs were calculated for sensitivity and specificity for each study and for the different molecular tests (Xpert MTB/RIF, Xpert Ultra MTB/RIF [Cepheid, Sunnyvale, CA, USA], and other tests) versus a reference standard (culture only, any bacteriological confirmation, and tuberculosis case definition). Sensitivity and specificity were stratified by the stool processing method. We also quantified the additionality of stool Xpert Ultra tests for tuberculosis bacteriological confirmation. The protocol was registered with PROSPERO, CRD42022341514. A total of 4521 records were identified through the database search, one record was identified from an article bibliography, and 67 studies were retained for full-text reading. 39 studies were included in the qualitative synthesis, 35 of which were included in the meta-analyses. When using any bacteriological confirmation from a respiratory sample as the reference standard, stool Xpert sensitivity was 0·60 (95% CI 0·48-0·71), stool Xpert Ultra sensitivity was 0·73 (0·63-0·81), and sensitivity was 0·44 (0·29-0·60) for other in-house molecular methods combined. When using tuberculosis case definition as the reference standard, stool Xpert sensitivity was 0·23 (0·11-0·41), stool Xpert Ultra sensitivity was 0·38 (0·22-0·56), and sensitivity was 0·17 (0·09-0·23) for other in-house molecular methods. The addition of stool Xpert Ultra increased bacteriological confirmation of tuberculosis by 38·6% overall. Further, the utilisation of centrifuge-free simplified methods improved the sensitivity of stool Xpert Ultra when using any bacteriological confirmation as a reference standard (0·77 [0·66-0·85] for centrifuge-free methods vs 0·61 [0·41-0·78] for non-centrifuge-free methods). This systematic review and meta-analysis supports the use of Xpert Ultra in stool samples as a diagnostic tool for paediatric tuberculosis diagnosis. Stool-based Xpert Ultra can contribute to increase the bacteriological confirmation in this population, even when respiratory specimens are also tested. The EDCTP2 programme supported by the EU via Stool4TB Project and the European Society of Pediatric Infectious Diseases.

Introduction: COVID‐19 stretched healthcare systems to their limits, particularly in settings with a pre‐existing high burden of infectious diseases, including HIV and tuberculosis (TB). We studied the impact of COVID‐19 on TB services at antiretroviral therapy (ART) clinics in low‐ and middle‐income countries.Methods: We surveyed ART clinics providing TB services in the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium in Africa and the Asia‐Pacific until July 2021 (TB diagnoses until the end of 2021). We collected site‐level data using standardized questionnaires.Results: Of 46 participating ART clinics, 32 (70%) were in Africa and 14 (30%) in the Asia‐Pacific; 52% provided tertiary care. Most clinics (85%) reported disrupted routine HIV care services during the pandemic, both in Africa (84%) and the Asia‐Pacific (86%). The most frequently reported impacts were on staff (52%) and resource shortages (37%; protective clothing, face masks and disinfectants). Restrictions in TB health services were observed in 12 clinics (26%), mainly reduced access to TB diagnosis and postponed follow‐up visits (6/12, 50% each), and restrictions in TB laboratory services (22%). Restrictions of TB services were addressed by dispensing TB drugs for longer periods than usual (7/12, 58%), providing telehealth services (3/12, 25%) and with changes in directly observed therapy (DOT) (e.g. virtual DOT, 3/12). The number of TB diagnoses at participating clinics decreased by 21% in 2020 compared to 2019; the decline was more pronounced in tertiary than primary/secondary clinics (24% vs. 12%) and in sites from the Asia‐Pacific compared to Africa (46% vs. 14%). In 2021, TB diagnoses continued to decline in Africa (–8%) but not in the Asia‐Pacific (+62%) compared to 2020. During the pandemic, new infection control measures were introduced or intensified at the clinics, including wearing face masks, hand sanitation and patient triage.Conclusions: The COVID‐19 pandemic led to staff shortages, reduced access to TB care and delays in follow‐up visits for people with TB across IeDEA sites in Africa and the Asia‐Pacific. Increased efforts are needed to restore and secure ongoing access to essential TB services in these contexts.