Brittney Sweetser

Background: Accurate nonsputum tests are essential for improving tuberculosis (TB) detection. We report the first evaluation of the Xpert TB/LTBI assay (research-use-only; Cepheid, USA), which detects 9 Mycobacterium tuberculosis antigen-stimulated mRNA targets from blood. Methods: We enrolled individuals ≥12 years with presumptive TB from clinics in Uganda and Vietnam. All participants underwent sputum- (liquid culture; Xpert MTB/RIF Ultra) and blood-based (Xpert TB/LTBI; QuantiFERON-TB Gold Plus [QFT-Plus]) testing. Participants were classified as having active TB (positive sputum results), latent TB infection (LTBI; positive QFT-Plus with negative sputum results), or no TB infection. Diagnostic accuracy for active TB (primary analysis) and of a 2-step algorithm that first predicted TB infection (active TB or LTBI) and then distinguished active TB from LTBI was assessed using logistic regression and receiver operating characteristic analysis. Results: Among 214 participants included, 56.5% were male, 9.3% were living with HIV, 29.0% had active TB, and 31.8% had LTBI. Xpert TB/LTBI area under the curve (AUC) was 0.92 (95% CI: .88–.96) for identifying active TB, and sensitivity was 93.5% (95% CI: 84.6–97.5) and specificity 76.3% (95% CI: 69.0–82.4) at a cut-point that achieved ≥90% sensitivity. In the 2-step algorithm, Xpert TB/LTBI had high accuracy for identifying TB infection in the first step, but accuracy was lower for distinguishing active TB from LTBI in the second step. Conclusions: Xpert TB/LTBI exceeded World Health Organization (WHO)-recommended minimum accuracy targets for a TB screening test. However, further refinement is needed to improve its ability to distinguish active TB from LTBI.

Background: Children with non-severe TB may benefit from short-course treatment, but point-of-care tools are needed to stratify disease severity. We prospectively evaluated the Cepheid Xpert MTB-Host Response (HR) prototype cartridge for distinguishing TB severity in children with pulmonary TB (PTB) in The Gambia and Uganda. Methods: We included children <15 with microbiologically confirmed or clinically diagnosed unconfirmed PTB. Severity was defined using the World Health Organization (WHO) guidelines for a four-month, drug-susceptible regimen. Capillary or venous blood was tested with the HR cartridge for PCR-based detection of 3 mRNA genes and calculation of a TB score from cycle thresholds. We generated receiver operating characteristic curves with the TB score to classify severe TB and assessed if Xpert-HR could achieve the WHO target accuracy for treatment optimization (≥90% sensitivity, ≥70% specificity). Results: Among 106 children, the median age was 4 years (IQR 1-7), 56.6% were female, and 13.2% were living with HIV. In all children with PTB, Xpert-HR achieved an AUC of 0.67 (95% CI 0.55-0.78), with 89.3% sensitivity (95% CI 71.8-97.7) and 29.5% specificity (95% CI 19.7-40.9, cutoff ≤ −0.60). By confirmation status, Xpert-HR approached the target accuracy in children with Confirmed TB, with 62.5% specificity (95% CI 24.5-91.5) at 91.7% sensitivity (95% CI 61.5-99.8, cut-off ≤ −1.349). Among children with Unconfirmed TB, specificity was lower (24.3%, 95% CI 14.8-36.0) at 93.8% sensitivity (95% CI 69.8-99.8, cutoff ≤ −0.450). Target accuracy was almost achieved in children 5-9 regardless of confirmation status (100% sensitivity [95% CI 71.5-100], 66.7% specificity [95% CI 43.0-85.4], cutoff ≤ −1.35), but specificity (28.2%, 95% CI 18.6-39.5) was lower for children < 5 (92.9% sensitivity, 95% CI 76.5-99.1, cutoff ≤ −0.550). Conclusions: Xpert-HR approached the target accuracy to stratify PTB severity in older children and those with Confirmed TB but had lower specificity in children with Unconfirmed TB. Child-specific signatures may be needed to improve performance in younger children with paucibacillary disease.

Childhood and adolescent cancer survivors (CACS) are a high-risk population for non-communicable diseases and secondary carcinogenesis. The Environmental and Community Health Program for Longitudinal Follow-up of CACS in the region of Murcia, Spain, is an ongoing pioneering program that constitutes a model for social innovation. This study aims to present the program tools and protocol as a whole, as well as a profile of the incidence, survival, and spatiotemporal distribution of childhood cancer in the region of Murcia, Spain, using 822 sample cases of cancer diagnosed in children under 15 years of age (1998–2020). While the crude incidence rate across that entire period was 149.6 per 1 million, there was an increase over that time in the incidence. The areas with a higher standardized incidence ratio have shifted from the northwest (1998-2003) to the southeast (2016–2020) region. Overall, the ten-year survival rate for all tumor types was 80.1% over the entire period, increasing the five-year survival rate from 76.1 (1998–2003) to 85.5 (2014–2018). CACS living in areas with very poor outdoor air quality had lower survival rates. Furthermore, integrating environmental health into clinical practice could improve knowledge of the etiology and prognosis, as well as the outcomes of CACS. Finally, monitoring individual carbon footprints and creating healthier lifestyles, alongside healthier environments for CACS, could promote wellbeing, environmental awareness, and empowerment in order to attain Sustainable Development Goals for non-communicable diseases in this population.