A CD8+ T cell diagnostic to identify children with pulmonary tuberculosis
DMID Protocol Number: 13-0018
Sponsor - U.S. National Institutes of Health (R44A1091267)
Principal Investigator - Deborah A. Lewinsohn, M.D., Viti Inc.
|Type of Study||Observational Study|
|Design||An observational study to test the sensitivity and specificity of a new immunodiagnostic blood test for tuberculosis ( ViTi ONE and ViTi TWO)|
|Project Site||Kampala, Uganda|
|Sample Size||Proposed, 284 subjects; Final Enrollment 247|
|Population||Children less than 5 years of age hospitalized with pneumonia|
|Study Period||September 2014 - March 2015|
|Interactions with TBRU||Collaborating investigators/staff, utilizing shared infrastructure|
Tuberculosis (TB) disease, which results from infection with Mycobacterium tuberculosis (Mtb), is a leading cause of infectious morbidity and mortality in children < 5 years old worldwide. In TB endemic regions, in which the vast majority of the world’s annual 9 million adult cases of TB disease reside, children < 5 years old account for 30–40% of the total patients and those children who are infected tend to have more severe, often fatal forms of TB. A significant contributor to the deadliness of TB in children < 5 years old is the poor performance of standard TB diagnostics in this age group, especially as compared to adults. Poor diagnostics result in delayed and missed diagnoses, which in turn lead to increased morbidity and mortality in children.
Currently, what is needed is a simple, robust immunodiagnostic blood test that will differentiate childhood TB pneumonia from pneumonia not due to TB. We hypothesize that the detection of CD8+ Tcells directed toward Mtb peptides can be utilized to distinguish young children with TB pneumonia from those with pneumonia not due to TB. In this regard, CD8+T cells preferentially recognize heavily Mtb-infected cells have been observed in Ugandan children < 5 years old, that Mtb-reactive CD8+Tcells are detected in children with TB and not detected in asymptomatic children with Mtb infection/exposure. Taken together, these data suggest that CD8+ T cells correlate with bacterial burden. ViTi Inc. investigators in collaboration with Oregon Health and Science University have developed a prototype immunodiagnostic blood test to detect these differences. These studies will further develop specificity and sensitivity of ViTi Inc.’s new immunodiagnostic blood test and validate it in a cohort of Ugandan children < 5 years old hospitalized with pneumonia.