Effect of isoniazid preventive therapy on immune responses to mycobacterium tuberculosis: an open label randomised, controlled, exploratory study

BMC Infectious Diseases

Research Article

Frederic Toulza¹  Hazel M. Dockrell¹  Steven G. Smith¹  Moses Egesa²  Simon Kimuda²  Irene Andia Biraro²  Moses Joloba²  Achilles Katamba²  Alison M Elliott³  Stephen Cose³  Jonathan Levin⁴ 

[1] Department of Immunology and Infection, London School of Hygiene &Tropical Medicine, London, UK;Department of Internal Medicine, College of Health Sciences, Makerere University, P.O Box 7072, Kampala, Uganda;Medical Research Council/Uganda Virus Research Institute, Uganda Research Unit on AIDS, Entebbe, Uganda;Department of Clinical Research, London School of Hygiene &Tropical Medicine, London, UK;Medical Research Council/Uganda Virus Research Institute, Uganda Research Unit on AIDS, Entebbe, Uganda;School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;

关键词: Latent tuberculosis infection;    Household contacts;    Randomised design;    Cytokines;    Antibodies;    Isoniazid preventive therapy;   

DOI  :  10.1186/s12879-015-1201-8

 received in 2015-05-25, accepted in 2015-10-12,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundWith 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.MethodsHousehold 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.ResultsSixteen 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.ConclusionsIPT 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.Trial registrationISRCTN registry, ISRCTN15705625. Registered on 30th September 2015.

【 授权许可】

CC BY   
© Biraro et al. 2015