Article Text
Abstract
Background Accurate diagnosis of latent tuberculosis infection (LTBI) in recently exposed HIV-infected tuberculosis (TB) contacts is a public health priority because of the high risk of progression to active TB but is hampered by the high background prevalence of LTBI in high-burden populations and poor sensitivity of tuberculin skin testing (TST) in HIV co-infection.
Methods The prevalence of LTBI in 222 recent household contacts of TB cases and 176 household contacts of community controls without TB in Harare, Zimbabwe were compared using TST and interferon γ enzyme-linked immunospot (ELISpot) responses to ESAT-6 (early secretory antigenic target-6) and CFP-10 (culture filtrate protein-10). TST and ELISpot results were correlated with markers of recent TB exposure and the impact of HIV co-infection was assessed.
Results In this high-incidence population, the proportion of ELISpot-positive contacts was not significantly different from community controls. However, ELISpot, unlike TST, revealed a higher prevalence of LTBI in recent contacts of sputum smear-positive cases than in contacts of controls. ELISpot results correlated significantly with positive sputum smear and culture status of the index case (adjusted OR 2.40, CI 1.12 to 5.14), even in the subgroup of HIV-infected contacts (adjusted OR 5.36, CI 1.11 to 25.93). and were independent of contacts' HIV status. TST results were also associated with positive smear and culture status of the index case (adjusted OR 4.41, CI 1.82 to 10.67) but were negatively associated with contacts' HIV status (adjusted OR 0.25, CI 0.10 to 0.60).
Conclusions Contact investigations in high-burden populations should focus on contacts of sputum smear-positive cases in whom recent infection can be detected by ELISpot, even in the presence of HIV co-infection.
- Enzyme-linked immunospot (ELISpot)
- HIV
- infection control
- interferon γ release assay
- tuberculin skin test
- tuberculosis
- viral infection
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Footnotes
JM and KAM contributed equally to this work.
Funding This study was funded by the Wellcome Trust. ELC is supported by a Wellcome Trust Senior Fellowship in Clinical Tropical Medicine and AL is supported by a Wellcome Trust Senior Research Fellowship in Clinical Science and a National Institute of Health Research Senior Investigator Award. The Wellcome Trust had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
Competing interests AL and KAM are inventors of patents relating to T cell-based diagnosis. The Lalvani ELISpot was commercialised by an Oxford University spin-out company (T-SPOT.TB, Oxford Immunotec, Abingdon, UK) in which Oxford University and AL have minority shares of equity and to which AL acted as non-executive director from 2003 to 2007. All other authors declare that they have no conflict of interest.
Ethics approval The study was approved by the ethics committees of the London School of Hygiene and Tropical Medicine, the Biomedical Research and Training Institute and the Medical Research Council of Zimbabwe.
Provenance and peer review Not commissioned; externally peer reviewed.