Diagnostic accuracy of a three-gene Mycobacterium tuberculosis host response cartridge using fingerstick blood for childhood tuberculosis: a multicentre prospective study in low-income and middle-income countries.

BACKGROUND: Childhood tuberculosis remains a major cause of morbidity and mortality in part due to missed diagnosis. Diagnostic methods with enhanced sensitivity using easy-to-obtain specimens are needed. We aimed to assess the diagnostic accuracy of the Cepheid Mycobacterium tuberculosis Host Response prototype cartridge (MTB-HR), a candidate test measuring a three-gene transcriptomic signature from fingerstick blood, in children with presumptive tuberculosis disease. METHODS: RaPaed-TB was a prospective diagnostic accuracy study conducted at four sites in African countries (Malawi, Mozambique, South Africa, and Tanzania) and one site in India. Children younger than 15 years with presumptive pulmonary or extrapulmonary tuberculosis were enrolled between Jan 21, 2019, and June 30, 2021. MTB-HR was performed at baseline and at 1 month in all children and was repeated at 3 months and 6 months in children on tuberculosis treatment. Accuracy was compared with tuberculosis status based on standardised microbiological, radiological, and clinical data. FINDINGS: 5313 potentially eligible children were screened, of whom 975 were eligible. 784 children had MTB-HR test results, of whom 639 had a diagnostic classification and were included in the analysis. MTB-HR differentiated children with culture-confirmed tuberculosis from those with unlikely tuberculosis with a sensitivity of 59·8% (95% CI 50·8-68·4). Using any microbiological confirmation (culture, Xpert MTB/RIF Ultra, or both), sensitivity was 41·6% (34·7-48·7), and using a composite clinical reference standard, sensitivity was 29·6% (25·4-34·2). Specificity for all three reference standards was 90·3% (95% CI 85·5-94·0). Performance was similar in different age groups and by malnutrition status. Among children living with HIV, accuracy against the strict reference standard tended to be lower (sensitivity 50·0%, 15·7-84·3) compared with those without HIV (61·0%, 51·6-69·9), although the difference did not reach statistical significance. Combining baseline MTB-HR result with one Ultra result identified 71·2% of children with microbiologically confirmed tuberculosis. INTERPRETATION: MTB-HR showed promising diagnostic accuracy for culture-confirmed tuberculosis in this large, geographically diverse, paediatric cohort and hard-to-diagnose subgroups. FUNDING: European and Developing Countries Clinical Trials Partnership, UK Medical Research Council, Swedish International Development Cooperation Agency, Bundesministerium für Bildung und Forschung; German Center for Infection Research (DZIF).

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.

Chest Imaging for Pulmonary TB-An Update.

The diagnosis of pulmonary tuberculosis (PTB) in children is challenging. Difficulties in acquiring suitable specimens, pauci-bacillary load, and limitations of current diagnostic methods often make microbiological confirmation difficult. Chest imaging provides an additional diagnostic modality that is frequently used in clinical practice. Chest imaging can also provide insight into treatment response and identify development of disease complications. Despite widespread use, chest radiographs are usually non-specific and have high inter- and intra-observer variability. Other diagnostic imaging modalities such as ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) can provide additional information to substantiate diagnosis. In this review, we discuss the radiological features of PTB in each modality, highlighting the advantages and limitations of each. We also address newer imaging technologies and potential use.

Asthma in South African adolescents: a time trend and risk factor analysis over two decades.

BACKGROUND: South Africa has undergone major economic and health system changes, impacting the epidemiology of childhood asthma. This study aimed to investigate prevalence time trends of asthma in South African adolescents over two decades and to identify associated risk factors. METHODS: A cross-sectional survey was conducted in 2017, in a randomised sample of 13-14-year-old Cape Town adolescents, using the standardised Global Asthma Network written, video and environmental questionnaires. Using time-trend analysis, the prevalence and severity of asthma were compared with data from the 2002 ISAAC phase III study. Environmental and social risk factors were analysed. RESULTS: A total of 3979 adolescents were included. The prevalence of lifetime and current asthma were 34.5% and 21.3%, respectively, on the self-report written questionnaire, similar to 2002 results. The prevalence of severe asthma in the previous 12 months increased, measured by wheeze limiting speech (7.8% to 11.8%), four or more attacks of wheezing (5.0% to 5.8%) or woken by wheeze on one or more nights per week (5.0% to 6.9%). The video questionnaire revealed increases in lifetime (16.9% to 22.5%), current (11.2% to 18.7%) and severe asthma (12.1% to 14.8%). Multivariate analysis showed associations between current asthma and smoking, female sex, pet exposure and higher socioeconomic status. Severe asthma was associated with smoking, pet exposure, outdoor pollution exposure and informal housing; 33% of those with severe or current asthma had been diagnosed. CONCLUSION: The prevalence of asthma is high, with increasing rates of severe asthma in adolescents. Underdiagnosis is a major concern and reduction in exposure to environmental factors, particularly smoking, and improved socioeconomic development are needed.