Kinetics of Mycobacterium tuberculosis-specific IFN-γ responses and sputum bacillary clearance in HIV-infected adults during treatment of pulmonary tuberculosis

David T. Mzinza; Derek James Sloan; Kondwani C. Jambo; Doris Shani; Mercy Kamdolozi; Katalin A. Wilkinson; Robert J. Wilkinson; Geraint R. Davies; Robert S. Heyderman; Henry C. Mwandumba

doi:10.1016/j.tube.2015.05.009

Kinetics of Mycobacterium tuberculosis-specific IFN-γ responses and sputum bacillary clearance in HIV-infected adults during treatment of pulmonary tuberculosis

David T. Mzinza, Derek James Sloan, Kondwani C. Jambo, Doris Shani, Mercy Kamdolozi, Katalin A. Wilkinson, Robert J. Wilkinson, Geraint R. Davies, Robert S. Heyderman, Henry C. Mwandumba^*

^*Corresponding author for this work

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

In HIV-uninfected adults with pulmonary tuberculosis (TB), anti-TB treatment is associated with changes in Mycobacterium tuberculosis (Mtb)-specific immune responses, which correlate with sputum bacillary load. It is unclear if this occurs in HIV-infected TB patients. We investigated changes in Mtb-specific immune responses and sputum bacillary clearance during anti-TB treatment in HIV-infected and HIV-uninfected adults with pulmonary TB. Sputum bacillary load was assessed by smear microscopy and culture. Mtb-specific IFN-γ secreting peripheral blood mononuclear cells were enumerated using an ELISPOT assay following stimulation with PPD, ESAT-6 and CFP-10. The baseline frequency of Mtb-specific IFN-γ secreting cells was lower in HIV-infected than HIV-uninfected patients (median PPD 32 vs. 104 Spot Forming Units (SFU), p = 0.05; CFP-10 19 vs. 74 SFU, p = 0.01). ESAT-6-specific IFN-γ secreting cells and sputum bacillary load declined progressively during treatment in both HIV-infected and HIV-uninfected patients. HIV infection did not influence the 2-month sputum culture conversion rate (Odds Ratio 0.89, p = 0.95). These findings suggest that changes in ESAT-6-specific immune responses during anti-TB treatment correspond with changes in sputum bacillary load irrespective of host HIV infection status. The utility of Mtb-specific IFN-γ responses as a proxy measure of treatment response in HIV-infected TB patients warrants further evaluation in other settings.

Original language	English
Article number	1343
Pages (from-to)	463-469
Number of pages	7
Journal	Tuberculosis
Volume	95
Issue number	4
Early online date	28 May 2015
DOIs	https://doi.org/10.1016/j.tube.2015.05.009
Publication status	Published - 1 Jul 2015

Keywords

Mycobacterium tuberculosis
Antigen-specific immunity
IFN-γ
Pulmonary tuberculosis
HIV infection
Anti-tuberculosis treatment

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.tube.2015.05.009Licence: CC BY

Sloan_2015_TreatmentPulmonaryTuberculosis_Tuberculosis_CC
© 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Final published version, 619 KBLicence: CC BY

Cite this

Mzinza, D. T., Sloan, D. J., Jambo, K. C., Shani, D., Kamdolozi, M., Wilkinson, K. A., Wilkinson, R. J., Davies, G. R., Heyderman, R. S., & Mwandumba, H. C. (2015). Kinetics of Mycobacterium tuberculosis-specific IFN-γ responses and sputum bacillary clearance in HIV-infected adults during treatment of pulmonary tuberculosis. Tuberculosis, 95(4), 463-469. Article 1343. https://doi.org/10.1016/j.tube.2015.05.009

@article{6d5a22b6159040b4a19b3ad491a66511,

title = "Kinetics of Mycobacterium tuberculosis-specific IFN-γ responses and sputum bacillary clearance in HIV-infected adults during treatment of pulmonary tuberculosis",

abstract = "In HIV-uninfected adults with pulmonary tuberculosis (TB), anti-TB treatment is associated with changes in Mycobacterium tuberculosis (Mtb)-specific immune responses, which correlate with sputum bacillary load. It is unclear if this occurs in HIV-infected TB patients. We investigated changes in Mtb-specific immune responses and sputum bacillary clearance during anti-TB treatment in HIV-infected and HIV-uninfected adults with pulmonary TB. Sputum bacillary load was assessed by smear microscopy and culture. Mtb-specific IFN-γ secreting peripheral blood mononuclear cells were enumerated using an ELISPOT assay following stimulation with PPD, ESAT-6 and CFP-10. The baseline frequency of Mtb-specific IFN-γ secreting cells was lower in HIV-infected than HIV-uninfected patients (median PPD 32 vs. 104 Spot Forming Units (SFU), p = 0.05; CFP-10 19 vs. 74 SFU, p = 0.01). ESAT-6-specific IFN-γ secreting cells and sputum bacillary load declined progressively during treatment in both HIV-infected and HIV-uninfected patients. HIV infection did not influence the 2-month sputum culture conversion rate (Odds Ratio 0.89, p = 0.95). These findings suggest that changes in ESAT-6-specific immune responses during anti-TB treatment correspond with changes in sputum bacillary load irrespective of host HIV infection status. The utility of Mtb-specific IFN-γ responses as a proxy measure of treatment response in HIV-infected TB patients warrants further evaluation in other settings.",

keywords = "Mycobacterium tuberculosis, Antigen-specific immunity, IFN-γ, Pulmonary tuberculosis, HIV infection, Anti-tuberculosis treatment",

author = "Mzinza, {David T.} and Sloan, {Derek James} and Jambo, {Kondwani C.} and Doris Shani and Mercy Kamdolozi and Wilkinson, {Katalin A.} and Wilkinson, {Robert J.} and Davies, {Geraint R.} and Heyderman, {Robert S.} and Mwandumba, {Henry C.}",

note = "This work was supported by funding from the Wellcome Trust (UK) through Fellowships 092773/Z/10/Z (to D.T.M), 086757/Z/08/Z (to D.J.S) and 088696/Z/09/Z (to H.C.M). Core funding from the Wellcome Trust supports the laboratory and office facilities at the Malawi-Liverpool-Wellcome Trust Clinical Research Programme.",

year = "2015",

month = jul,

day = "1",

doi = "10.1016/j.tube.2015.05.009",

language = "English",

volume = "95",

pages = "463--469",

journal = "Tuberculosis",

issn = "1472-9792",

publisher = "Elsevier Inc.",

number = "4",

}

Mzinza, DT, Sloan, DJ, Jambo, KC, Shani, D, Kamdolozi, M, Wilkinson, KA, Wilkinson, RJ, Davies, GR, Heyderman, RS & Mwandumba, HC 2015, 'Kinetics of Mycobacterium tuberculosis-specific IFN-γ responses and sputum bacillary clearance in HIV-infected adults during treatment of pulmonary tuberculosis', Tuberculosis, vol. 95, no. 4, 1343, pp. 463-469. https://doi.org/10.1016/j.tube.2015.05.009

TY - JOUR

T1 - Kinetics of Mycobacterium tuberculosis-specific IFN-γ responses and sputum bacillary clearance in HIV-infected adults during treatment of pulmonary tuberculosis

AU - Mzinza, David T.

AU - Sloan, Derek James

AU - Jambo, Kondwani C.

AU - Shani, Doris

AU - Kamdolozi, Mercy

AU - Wilkinson, Katalin A.

AU - Wilkinson, Robert J.

AU - Davies, Geraint R.

AU - Heyderman, Robert S.

AU - Mwandumba, Henry C.

N1 - This work was supported by funding from the Wellcome Trust (UK) through Fellowships 092773/Z/10/Z (to D.T.M), 086757/Z/08/Z (to D.J.S) and 088696/Z/09/Z (to H.C.M). Core funding from the Wellcome Trust supports the laboratory and office facilities at the Malawi-Liverpool-Wellcome Trust Clinical Research Programme.

PY - 2015/7/1

Y1 - 2015/7/1

N2 - In HIV-uninfected adults with pulmonary tuberculosis (TB), anti-TB treatment is associated with changes in Mycobacterium tuberculosis (Mtb)-specific immune responses, which correlate with sputum bacillary load. It is unclear if this occurs in HIV-infected TB patients. We investigated changes in Mtb-specific immune responses and sputum bacillary clearance during anti-TB treatment in HIV-infected and HIV-uninfected adults with pulmonary TB. Sputum bacillary load was assessed by smear microscopy and culture. Mtb-specific IFN-γ secreting peripheral blood mononuclear cells were enumerated using an ELISPOT assay following stimulation with PPD, ESAT-6 and CFP-10. The baseline frequency of Mtb-specific IFN-γ secreting cells was lower in HIV-infected than HIV-uninfected patients (median PPD 32 vs. 104 Spot Forming Units (SFU), p = 0.05; CFP-10 19 vs. 74 SFU, p = 0.01). ESAT-6-specific IFN-γ secreting cells and sputum bacillary load declined progressively during treatment in both HIV-infected and HIV-uninfected patients. HIV infection did not influence the 2-month sputum culture conversion rate (Odds Ratio 0.89, p = 0.95). These findings suggest that changes in ESAT-6-specific immune responses during anti-TB treatment correspond with changes in sputum bacillary load irrespective of host HIV infection status. The utility of Mtb-specific IFN-γ responses as a proxy measure of treatment response in HIV-infected TB patients warrants further evaluation in other settings.

AB - In HIV-uninfected adults with pulmonary tuberculosis (TB), anti-TB treatment is associated with changes in Mycobacterium tuberculosis (Mtb)-specific immune responses, which correlate with sputum bacillary load. It is unclear if this occurs in HIV-infected TB patients. We investigated changes in Mtb-specific immune responses and sputum bacillary clearance during anti-TB treatment in HIV-infected and HIV-uninfected adults with pulmonary TB. Sputum bacillary load was assessed by smear microscopy and culture. Mtb-specific IFN-γ secreting peripheral blood mononuclear cells were enumerated using an ELISPOT assay following stimulation with PPD, ESAT-6 and CFP-10. The baseline frequency of Mtb-specific IFN-γ secreting cells was lower in HIV-infected than HIV-uninfected patients (median PPD 32 vs. 104 Spot Forming Units (SFU), p = 0.05; CFP-10 19 vs. 74 SFU, p = 0.01). ESAT-6-specific IFN-γ secreting cells and sputum bacillary load declined progressively during treatment in both HIV-infected and HIV-uninfected patients. HIV infection did not influence the 2-month sputum culture conversion rate (Odds Ratio 0.89, p = 0.95). These findings suggest that changes in ESAT-6-specific immune responses during anti-TB treatment correspond with changes in sputum bacillary load irrespective of host HIV infection status. The utility of Mtb-specific IFN-γ responses as a proxy measure of treatment response in HIV-infected TB patients warrants further evaluation in other settings.

KW - Mycobacterium tuberculosis

KW - Antigen-specific immunity

KW - IFN-γ

KW - Pulmonary tuberculosis

KW - HIV infection

KW - Anti-tuberculosis treatment

U2 - 10.1016/j.tube.2015.05.009

DO - 10.1016/j.tube.2015.05.009

M3 - Article

AN - SCOPUS:84931576581

SN - 1472-9792

VL - 95

SP - 463

EP - 469

JO - Tuberculosis

JF - Tuberculosis

IS - 4

M1 - 1343

ER -

Kinetics of Mycobacterium tuberculosis-specific IFN-γ responses and sputum bacillary clearance in HIV-infected adults during treatment of pulmonary tuberculosis

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this