Interpretation of serial interferon-gamma test results to measure new tuberculosis infection among household contacts in
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RESEARCH ARTICLE
Open Access
Interpretation of serial interferon-gamma test results to measure new tuberculosis infection among household contacts in Zambia and South Africa Rosa Sloot1* , Kwame Shanaube2, Mareli Claassens1, Lily Telisinghe3, Ab Schaap2, Peter Godfrey-Faussett4,5, Helen Ayles2,5 and Sian Floyd6
Abstract Background: A more stringent QuantiFERON-TB Gold In-Tube (QFT) conversion (from negative to positive) definition has been proposed to allow more definite detection of recent tuberculosis (TB) infection. We explored alternative conversion definitions to assist the interpretation of serial QFT results and estimate incidence of TB infection in a large cohort study. Methods: We used QFT serial results from TB household contacts aged ≥15 years, collected at baseline and during two follow-up visits (2006–2011) as part of a cohort study in 24 communities in Zambia and South Africa (SA). Conversion rates using the manufacturers’ definition (interferon-gamma (IFN-g) < 0.35 to ≥0.35, ‘def1’) were compared with stricter definitions (IFN-g < 0.2 to ≥0.7 IU/ml, ‘def2’; IFN-g < 0.2 to ≥1.05 IU/ml, ‘def3’; IFN-g < 0.2 to ≥1.4 IU/ml, ‘def4’). Poisson regression was used for analysis. Results: One thousand three hundred sixty-five individuals in Zambia and 822 in SA had QFT results available. Among HIV-negative individuals, the QFT conversion rate was 27.4 per 100 person-years (CI:22.9–32.6) using def1, 19.0 using def2 (CI:15.2–23.7), 14.7 using def3 (CI:11.5–18.8), and 12.0 using def4 (CI:9.2–15.7). Relative differences across def1-def4 were similar in Zambia and SA. Using def1, conversion was less likely if HIV positive not on antiretroviral treatment compared to HIV negative (aRR = 0.7, 95%CI = 0.4–0.9), in analysis including both countries. The same direction of associations were found using def 2–4. Conclusion: High conversion rates were found even with the strictest definition, indicating high incidence of TB infection among household contacts of TB patients in these communities. The trade-off between sensitivity and specificity using different thresholds of QFT conversion remains unknown due to the absence of a reference standard. However, we identified boundaries within which an appropriate definition might fall, and our strictest definition plausibly has high specificity. Keywords: Conversion, Tuberculosis, QuantiFERON, Interferon-gamma
* Correspondence: [email protected] 1 Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third p
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