EDCTP Alumni Network

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All Profiles
Call Career Development Fellowship (CDF)
Programme EDCTP1
Start Date 2007-03-15
End Date 2010-07-01
Project Code TA.2005.40203.001
Status Completed

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.

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

Host Organisation

Institution Country
Medical Research Council Gambia

Participants

Name Institution Country
Richard Adegbola MRC Laboratories Gambia
Martin Antonio MRC Laboratories Gambia
Philip Hill MRC Laboratories Gambia

Study Design

Immunological studies in TB immunity

Sites

N/A

Phd Study

Title University Start Date End Date
Interferon Gamma Releaase Assays for Tuberculosis and their potential as efficacy markers for intervention trials University of Amsteram 2007-10-01 2012-10-12

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).

Publications

Adetifa IM et al. Mycobacterium tuberculosis Infection in close childhood contacts of adults with Pulmonary Tuberculosis is increased by Second-hand exposure to Tobacco. Am J Trop Med Hyg. 2017 Aug;97(2):429-432
Hill PC et al. Longitudinal assessment of an ELISPOT test for Mycobacterium tuberculosis infection. PLoS Med. 2007;4(6):e192
Adetifa IM et al. Commercial interferon gamma release assays compared to the tuberculin skin test for diagnosis of latent Mycobacterium tuberculosis infection in childhood contacts in the Gambia. Pediatr Infect Dis J. 2010;29(5):439-43
Adetifa IM et al. A Tuberculin Skin Test Survey and the Annual Risk of Mycobacterium tuberculosis Infection in Gambian School Children. PLoS One (2015) 10(10):e0139354
Buchwald, U.K et al. Broad Adaptive Immune Responses to M. tuberculosis Antigens Precede TST Conversion in Tuberculosis Exposed Household Contacts in a TB-Endemic Setting. PLoS One (2014) 9(12):e116268
Morter R et al. Examining human paragonimiasis as a differential diagnosis to tuberculosis in The Gambia. BMC Res Notes (2018) 11:31
Hill PC. Comparison of enzyme-linked immunospot assay and tuberculin skin test in healthy children exposed to Mycobacterium tuberculosis. Pediatrics. 2006;117(5):1542-8

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