Limits...
Impact of co-infections and BCG immunisation on immune responses among household contacts of tuberculosis patients in a Ugandan cohort.

Biraro IA, Egesa M, Toulza F, Levin J, Cose S, Joloba M, Smith S, Dockrell HM, Katamba A, Elliott AM - PLoS ONE (2014)

Bottom Line: Exploring other risk factors, Th1 cytokines among LTBI-positive HHCs with BCG scars were greatly reduced compared to those without scars: (adjusted geometric mean ratio) IFNγ 0.20 (0.09-0.42), <0.0001; IL-2 0.34 (0.20-0.59), <0.0001; and TNFα 0.36 (0.16-0.79), 0.01.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.

View Article: PubMed Central - PubMed

Affiliation: College of Health Sciences, Makerere University, Kampala, Uganda.

ABSTRACT

Background: 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 LTBI-positive HHCs with BCG scars were greatly reduced compared to those without scars: (adjusted geometric mean ratio) IFNγ 0.20 (0.09-0.42), <0.0001; IL-2 0.34 (0.20-0.59), <0.0001; and TNFα 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.

Show MeSH

Related in: MedlinePlus

Flow diagram showing the recruitment process.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4221037&req=5

pone-0111517-g001: Flow diagram showing the recruitment process.

Mentions: The study recruited 101 index cases and 291 HHCs who were followed up as detailed in figure 1.


Impact of co-infections and BCG immunisation on immune responses among household contacts of tuberculosis patients in a Ugandan cohort.

Biraro IA, Egesa M, Toulza F, Levin J, Cose S, Joloba M, Smith S, Dockrell HM, Katamba A, Elliott AM - PLoS ONE (2014)

Flow diagram showing the recruitment process.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4221037&req=5

pone-0111517-g001: Flow diagram showing the recruitment process.
Mentions: The study recruited 101 index cases and 291 HHCs who were followed up as detailed in figure 1.

Bottom Line: Exploring other risk factors, Th1 cytokines among LTBI-positive HHCs with BCG scars were greatly reduced compared to those without scars: (adjusted geometric mean ratio) IFNγ 0.20 (0.09-0.42), <0.0001; IL-2 0.34 (0.20-0.59), <0.0001; and TNFα 0.36 (0.16-0.79), 0.01.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.

View Article: PubMed Central - PubMed

Affiliation: College of Health Sciences, Makerere University, Kampala, Uganda.

ABSTRACT

Background: 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 LTBI-positive HHCs with BCG scars were greatly reduced compared to those without scars: (adjusted geometric mean ratio) IFNγ 0.20 (0.09-0.42), <0.0001; IL-2 0.34 (0.20-0.59), <0.0001; and TNFα 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.

Show MeSH
Related in: MedlinePlus