Thrasher Research Fund - Medical research grants to improve the lives of children

Project Details

Early Career

Status: Funded - Open

Novel Strategies to Improve Tuberculosis Case Finding in Children with Severe Acute Malnutrition

Bryan Vonasek, MD


BACKGROUND: Children with SAM are a key target population for TB case finding, but accurate diagnosis of TB in this population remains a major problem in resource-limited settings. GAP: Over the past few years, less-invasive methods of TB diagnosis (urine LAM, POCUS, stool Ultra) have shown promise in adults (and a growing evidence base for children as well) with severe immunosuppression secondary to HIV, given their tendency to develop disseminated and extrapulmonary TB. There is growing recognition of children with SAM as a key high-risk group for TB case finding, and given the relative immunosuppression in this population as well, these diagnostic strategies may complement each other for maximizing detection of pulmonary or extrapulmonary TB. HYPOTHESIS: This pilot work is not hypothesis driven. The study aim is to assess the diagnostic accuracy of urine FujiLAM, POCUS, and stool Ultra, individually and in combination, for TB in children with SAM <5 years of age. METHODS: This will be a cross-sectional observational study of consecutive patients admitted with SAM comparing the diagnostic accuracy of FujiLAM, POCUS, and stool Ultra, individually and in combination, to a microbiological reference standard (culture confirmation) and a composite reference standard (culture confirmation or clinical diagnosis). We will enroll inpatients with SAM ages 6 to 59 months at Kamuzu Central Hospital in Lilongwe, Malawi. RESULTS: From November 2021 to May 2022, 132 children were enrolled. Their mean age was 19 months, 27% had kwashiorkor, 5% were HIV infected, and 6% were HIV exposed. In-hospital mortality was 5%. Four (3%) were classified as ‘confirmed TB,’ 27 (20%) as ‘unconfirmed TB,’ and 101 (77%) as unlikely TB. Under routine care, 11 (8%) children were started on TB treatment. Urine FujiLAM testing will be done in the near future, and then final analyses will be conducted. IMPACT: This pilot project will provide valuable insight into the most accurate combinations of less invasive diagnostic strategies for TB in children with SAM, promoting future studies that will: 1) further detail diagnostic accuracy, 2) assess feasibility and cost-effectiveness in resource-limited settings, and 3) assess the impact of these diagnostics on patient-centered outcomes such as mortality with a randomized controlled trial.