Abstract
SummaryObjectivesBlood-based Interferon-Gamma Release Assays (IGRA) identify Mycobacterium tuberculosis (MTB) sensitisation with increased specificity, but sensitivity remains impaired in human immunodeficiency virus (HIV) infected persons. The QuantiFERON-TB Gold In-Tube test contains peptide 38–55 of Rv2654c, based on data indicating differential recognition between tuberculosis patients and BCG vaccinated controls in Europe. We aimed to fine map the T cell response to Rv2654c with the view of improving sensitivity.MethodsInterferon-gamma ELISpot assay was used in HIV uninfected persons with latent and active tuberculosis to map peptide epitopes of Rv2654c. A modified IGRA was tested in two further groups of 55 HIV uninfected and 44 HIV infected persons, recruited in South Africa.ResultsThe most prominently recognised peptide was between amino acids 51–65. Using p51-65 to boost the QuantiFERON-TB Gold In-Tube assay, the quantitative performance of the modified IGRA increased from 1.83 IU/ml (IQR 0.30–7.35) to 2.83 (IQR 0.28–12.2; p = 0.002) in the HIV uninfected group. In the HIV infected cohort the percentage of positive responders increased from 57% to 64% but only after 3 months of ART (p = ns).ConclusionsOur data shows the potential to population tailor detection of MTB sensitization using specific synthetic peptides and interferon-gamma release in vitro.
Highlights
Despite the worldwide availability of vaccination, diagnosis and treatment, tuberculosis (TB) is still a major global health problem and it is estimated that more than one-third of the world’s population is infected by Mycobacterium tuberculosis (MTB).[1]
Our data shows the potential to population tailor detection of MTB sensitization using specific synthetic peptides and interferon-gamma release in vitro. a 2015 The Authors
Exposure to MTB may result in latent TB infection (LTBI) which is defined by the absence of clinical TB symptoms but carries about 5e10% lifetime risk of developing active TB and comprises a significant reservoir of future cases of active disease, in countries with high human immunodeficiency virus (HIV) burdens.[2]
Summary
Despite the worldwide availability of vaccination, diagnosis and treatment, tuberculosis (TB) is still a major global health problem and it is estimated that more than one-third of the world’s population is infected by Mycobacterium tuberculosis (MTB).[1] Exposure to MTB may result in latent TB infection (LTBI) which is defined by the absence of clinical TB symptoms but carries about 5e10% lifetime risk of developing active TB and comprises a significant reservoir of future cases of active disease, in countries with high HIV burdens.[2] The estimated incidence of TB is 9 million each year, among which 1.5 million cases die. BCG vaccination renders the TB diagnosis more difficult as the commonly used tuberculin skin test (TST), based on the administration of purified protein derivative (PPD), may give false-positive results due to previous BCG immunization.[4]
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