Effect of isoniazid preventive therapy on immune responses to mycobacterium tuberculosis: an open label randomised, controlled, exploratory study
dc.contributor.author | Andia Biraro, Irene | |
dc.contributor.author | Egesa, Moses | |
dc.contributor.author | Kimuda, Simon | |
dc.contributor.author | Smith, Steven G. | |
dc.contributor.author | Toulza, Frederic | |
dc.contributor.author | Levin, Jonathan | |
dc.contributor.author | Joloba, Moses | |
dc.contributor.author | Katamba, Achilles | |
dc.contributor.author | Cose, Stephen | |
dc.contributor.author | Hazel M., Dockrell | |
dc.contributor.author | Elliott, Alison M. | |
dc.date.accessioned | 2023-01-18T15:35:05Z | |
dc.date.available | 2023-01-18T15:35:05Z | |
dc.date.issued | 2015 | |
dc.description.abstract | With the renewed emphasis to implement isoniazid preventive therapy (IPT) in Sub-Saharan Africa, we investigated the effect of IPT on immunological profiles among household contacts with latent tuberculosis. Methods: Household contacts of confirmed tuberculosis patients were tested for latent tuberculosis using the QuantiFERON®-TB Gold In-Tube (QFN) assay and tuberculin skin test (TST). HIV negative contacts aged above 5 years, positive to both QFN and TST, were randomly assigned to IPT and monthly visits or monthly visits only. QFN culture supernatants from enrolment and six months’ follow-up were analysed for M.tb-specific Th1, Th2, Th17, and regulatory cytokines by Luminex assay, and for M.tb-specific IgG antibody concentrations by ELISA. Effects of IPT were assessed as the net cytokine and antibody production at the end of six months. Results: Sixteen percent of contacts investigated (47/291) were randomised to IPT (n = 24) or no IPT (n = 23). After adjusting for baseline cytokine or antibody responses, and for presence of a BCG scar, IPT (compared to no IPT) resulted in a relative decline in M.tb-specific production of IFN gamma (adjusted mean difference at the end of six months (bootstrap 95 % confidence interval (CI), p-value) -1488.6 pg/ml ((−2682.5, −294.8), p = 0.01), and IL- 2 (−213.1 pg/ml (−419.2, −7.0), p = 0.04). A similar decline was found in anti-CFP-10 antibody levels (adjusted geometric mean ratio (bootstrap 95 % CI), p-value) 0.58 ((0.35, 0.98), p = 0.04). We found no effect on M.tb-specific Th2 or regulatory or Th17 cytokine responses, or on antibody concentrations to PPD and ESAT-6. Conclusions: IPT led to a decrease in Th1 cytokine production, and also in the anti CFP-10 antibody concentration. This could be secondary to a reduction in mycobacterial burden or as a possible direct effect of isoniazid induced T cell apoptosis, and may have implications for protective immunity following IPT in tuberculosis-endemic countries. | en_US |
dc.identifier.citation | Biraro, I. A., Egesa, M., Kimuda, S., Smith, S. G., Toulza, F., Levin, J., ... & Elliott, A. M. (2015). Effect of isoniazid preventive therapy on immune responses to mycobacterium tuberculosis: an open label randomised, controlled, exploratory study. BMC infectious diseases, 15(1), 1-12. DOI 10.1186/s12879-015-1201-8 | en_US |
dc.identifier.other | 10.1186/s12879-015-1201-8 | |
dc.identifier.uri | https://nru.uncst.go.ug/handle/123456789/7024 | |
dc.language.iso | en | en_US |
dc.publisher | BMC infectious diseases | en_US |
dc.subject | Latent tuberculosis infection | en_US |
dc.subject | Household contacts | en_US |
dc.subject | Randomised design | en_US |
dc.subject | Cytokines | en_US |
dc.subject | Antibodies | en_US |
dc.subject | Isoniazid preventive therapy | en_US |
dc.title | Effect of isoniazid preventive therapy on immune responses to mycobacterium tuberculosis: an open label randomised, controlled, exploratory study | en_US |
dc.type | Article | en_US |
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