Whole Blood Mycobacterial Growth Assays for Assessing Human Tuberculosis Susceptibility: A Systematic Review and Meta-Analysis

BackgroundWhole blood mycobacterial growth assays (WBMGA) quantify mycobacterial growth in fresh blood samples and may have potential for assessing tuberculosis vaccines and identifying individuals at risk of tuberculosis. We evaluated the evidence for the underlying assumption that in vitro WBMGA results can predict in vivo tuberculosis susceptibility.MethodsA systematic search was done for studies assessing associations between WBMGA results and tuberculosis susceptibility. Meta-analyses were performed for eligible studies by calculating population-weighted averages.ResultsNo studies directly assessed whether WBMGA results predicted tuberculosis susceptibility. 15 studies assessed associations between WBMGA results and proven correlates of tuberculosis susceptibility, which we divided in two categories. Firstly, WBMGA associations with factors believed to reduce tuberculosis susceptibility were statistically significant in all eight studies of: BCG vaccination; vitamin D supplementation; altitude; and HIV-negativity/therapy. Secondly, WBMGA associations with probable correlates of tuberculosis susceptibility were statistically significant in three studies of tuberculosis disease, in a parasitism study and in two of the five studies of latent tuberculosis infection. Meta-analyses for associations between WBMGA results and BCG vaccination, tuberculosis infection, tuberculosis disease and HIV infection revealed consistent effects. There was considerable methodological heterogeneity.ConclusionsThe study results generally showed significant associations between WBMGA results and correlates of tuberculosis susceptibility. However, no study directly assessed whether WBMGA results predicted actual susceptibility to tuberculosis infection or disease. We recommend optimization and standardization of WBMGA methodology and prospective studies to determine whether WBMGA predict susceptibility to tuberculosis disease.

Polymorphism in Toll-like Receptor 10 and Tuberculosis Susceptibility in Egyptian Population

Background: One-third of the world’s population is infected with Mycobacterium tuberculosis. Difference in clinical outcome of infection implies that host genetics may be implicated in such variability. Investigations of Toll-like receptors (TLRs) revealed new information regarding the immunopathogenesis of tuberculosis. Toll-like receptor 2 (TLR2) mediates crucial immune response against Mycobacterium tuberculosis. There is argument that Toll-like receptor (TLR10) participate in tuberculosis susceptibility by acting as a signaling modulator for TLR2. Objectives: The aim of this study was investigating the relationship between TLR 10 SNP 720A/C (rs11096957) and increase susceptibility to tuberculosis. Methodology: Eighty patients with radiological, microbiological and clinical proven active pulmonary tuberculosis (T.B) were included in this study. (TLR10) polymorphisms and allele distributions were compared between these 80 patients and 70 healthy control subjects. Peripheral blood samples were taken from all patients and controls. Genotyping was accomplished by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: When we compare T.B cases with controls, a statistically significant association was observed between T.B susceptibility and SNP 720A/C (rs11096957) in (TLR10). Allele (A) was more frequent in tuberculous cases while allele (C) was more common in controls. It was reported that the AA genotype of (TLR10) SNP rs11096957 was considerably related to the increased risk of developing pulmonary T.B. Homozygosity (AA) has been associated with predisposition to disease by comparing cases to controls (P = 0.045; OR = 2.0; 95% C.I. = 1.0- 4.0). A/C heterozygosity was considerably different in tuberculous cases than in healthy controls with lower risk of developing tuberculosis (P = 0.044; OR = 0.5; 95% C.I. = 0.26 –0.98). Conclusion: TLR10 SNP rs11096957 polymorphism is a risk factor for tuberculosis infection.