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Dr
Ifedayo Adetifa

South Africa

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Profile EDCTP Fellowship 1

Project Title

A double blind, placebo controlled randomized trial of vitamin A supplementation for modulation of Mycobacterium tuberculosis immune responses in children aged 5-14 years with latent Tuberculosis.

EDCTP Project

TA.2005.40203.001

EDCTP Program

EDCTP1

EDCTP Project Call

Career Development Fellowship (CDF)

Project Objectives

To provide additional evidence for the performance of novel diagnostics for latent tuberculosis and TB case detection in adults and children especially those with paucibacillary disease in a TB endemic country; and to identify differences in immune responses may improve our understanding of what constitutes protection against progression to TB in those latently infected

Study Design

Immunological studies in TB immunity

Host Organisation

Department Institution Country
Medical Research Council Medical Research Council ZA

Sites

Results & Outcomes

In a cross sectional study, the ELISPOT test was more sensitive than the QFT-GIT for diagnosing TB disease, but both tests performed similarly in the diagnosis of LTBI in TB contacts. In an extension of this study to two newly licensed commercial IGRAs, it was found that both IGRAs and the TST responded in a similar manner to a gradient of exposure to TB. In addition, each IGRA in combination with TST increased sensitivity for diagnosis of LTBI but was also associated with a loss of specificity. Also tested as Hain Sciences Line probe assay, MTBDRplus® in a 2 step-procedure. On 93 smear negative culture positive samples, the LPA had a sensitivity of 45.2% (42 of 93) and over half of the results were blank. There was no relationship between the results from post decontamination ZN concentration staining and failed LPA results. In assessing gene expression for cytokines protective against TB disease progression IFN-γ was significantly lower in progressors compared to both non-progressors and TB cases (p=0.0328 and p=0.0062 respectively). For other cytokines-IL-10 and IL-12 similar levels were seen between the groups. IL-18 was significantly higher in progressors compared to non-progressors and confirmed TB cases (p<0.001 for both).