Impact of Co-Infections and BCG Immunisation on Immune Responses among Household Contacts of Tuberculosis Patients in a Ugandan Cohort
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Date
2014
Journal Title
Journal ISSN
Volume Title
Publisher
PLoS ONE
Abstract
Tuberculosis incidence in resource poor countries remains high. We hypothesized that immune modulating
co-infections such as helminths, malaria, and HIV increase susceptibility to latent tuberculosis infection (LTBI), thereby
contributing to maintaining the tuberculosis epidemic.
Methods: Adults with sputum-positive tuberculosis (index cases) and their eligible household contacts (HHCs) were
recruited to a cohort study between May 2011 and January 2012. HHCs were investigated for helminths, malaria, and HIV at
enrolment. HHCs were tested using the QuantiFERON-TB Gold In-Tube (QFN) assay at enrolment and six months later.
Overnight whole blood culture supernatants from baseline QFN assays were analyzed for cytokine responses using an 11-
plex Luminex assay. Associations between outcomes (LTBI or cytokine responses) and exposures (co-infections and other
risk factors) were examined using multivariable logistic and linear regression models.
Results: We enrolled 101 index cases and 291 HHCs. Among HHCs, baseline prevalence of helminths was 9% (25/291),
malaria 16% (47/291), HIV 6% (16/291), and LTBI 65% (179/277). Adjusting for other risk factors and household clustering,
there was no association between LTBI and any co-infection at baseline or at six months: adjusted odds ratio (95%
confidence interval (CI); p-value) at baseline for any helminth, 1.01 (0.39–2.66; 0.96); hookworm, 2.81 (0.56–14.14; 0.20);
malaria, 1.06 (0.48–2.35; 0.87); HIV, 0.74 (0.22–2.47; 0.63). HHCs with LTBI had elevated cytokine responses to tuberculosis
antigens but co-infections had little effect on cytokine responses. Exploring other risk factors, Th1 cytokines among LTBIpositive
HHCs with BCG scars were greatly reduced compared to those without scars: (adjusted geometric mean ratio) IFNc
0.20 (0.09–0.42), ,0.0001; IL-2 0.34 (0.20–0.59), ,0.0001; and TNFa 0.36 (0.16–0.79), 0.01.
Conclusions: We found no evidence that co-infections increase the risk of LTBI, or influence the cytokine response profile
among those with LTBI. Prior BCG exposure may reduce Th1 cytokine responses in LTBI.
Description
Keywords
Co-Infections, BCG Immunisation, Immune Responses, Household Contacts, Tuberculosis Patients
Citation
Biraro IA, Egesa M, Toulza F, Levin J, Cose S, et al. (2014) Impact of Co-Infections and BCG Immunisation on Immune Responses among Household Contacts of Tuberculosis Patients in a Ugandan Cohort. PLoS ONE 9(11): e111517. doi:10.1371/journal.pone.0111517