ESPID Education. Hamilton S. 06/07/11; 7727
Dr. Shea Hamilton
Dr. Shea Hamilton

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S. Hamilton1, S. Anderson6, R. Heyderman2, B. Eley3, N. French4, H. Dockrell4, R. Wilkinson5, P. Langford1, M. Levin1 and the ILULU consortium

1Department of Paediatrics, Imperial College London, UK, 2 Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Malawi, 3Paediatric Infectious Diseases, Red Cross Children's Hospital, Cape Town, RSA, 4Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, UK, 5Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, RSA, 6Brighton & Sussex Medical School, Sussex University, UK

Background: Improved diagnosis of tuberculosis (TB) is essential for reducing the incidence of this disease in sub-Saharan Africa. Currently half of all cases of infectious TB are undiagnosed. This proportion is higher in children, as clinical features overlap those of many chronic infections and microbiological confirmation is complicated by paucibacillary load. The development of a rapid, sensitive and affordable serological diagnostic test for TB in children is urgently needed. Surface-Enhanced Laser Desorption Ionisation (SELDI) technology has been widely employed to identify serum based biomarkers in infectious diseases.

Methods: Serum samples (n=1000) were collected from children and adults (HIV-positive and HIV-negative) with active TB (culture confirmed), latent TB (IGRA+ and TST+) and controls (other infections and inflammatory conditions). Patients were recruited from two regions of sub-Saharan Africa with differing patterns of HIV, TB and malarial infection to ensure that the biomarker candidates would not be population specific. Serum proteomic profiles were obtained by SELDI using cation capture (CM10; pH 4.0 and 6.0), anion capture (Q10; pH 7.5 and 9.5) and immobilized metal affinity (IMAC30; Cu) ProteinChip™ arrays.

Results: SELDI analysis generated over 6000 serum protein profiles. Specific proteins were identified as statistically significant (P< 0.001) in distinguishing children with active TB from those with latent TB infection regardless of HIV status. Several of these potential biomarkers were observed in both children and adults.

Conclusions: A series of serum proteins have been found that will potentially enhance the diagnosis of TB in children. These are currently being identified at the molecular level.
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