Interpretation of serial interferon-gamma test results to measure new tuberculosis infection among household contacts in Zambia and South Africa.


Journal

BMC infectious diseases
ISSN: 1471-2334
Titre abrégé: BMC Infect Dis
Pays: England
ID NLM: 100968551

Informations de publication

Date de publication:
15 Oct 2020
Historique:
received: 13 04 2020
accepted: 06 10 2020
entrez: 16 10 2020
pubmed: 17 10 2020
medline: 13 11 2020
Statut: epublish

Résumé

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. 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. 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. 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.

Sections du résumé

BACKGROUND 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 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 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 CONCLUSIONS
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.

Identifiants

pubmed: 33059620
doi: 10.1186/s12879-020-05483-9
pii: 10.1186/s12879-020-05483-9
pmc: PMC7559914
doi:

Substances chimiques

Anti-Retroviral Agents 0

Types de publication

Journal Article Multicenter Study Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

760

Subventions

Organisme : Medical Research Council
ID : MR/N020618/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R010161/1
Pays : United Kingdom
Organisme : European and Developing Countries Clinical Trials Partnership
ID : MR/R010161/1
Organisme : Johns Hopkins University
ID : 19790.01

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Auteurs

Rosa Sloot (R)

Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. sloot.rosa@gmail.com.

Kwame Shanaube (K)

Zambart, School of Medicine, University of Zambia, Lusaka, Zambia.

Mareli Claassens (M)

Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

Lily Telisinghe (L)

School of Social and Community Medicine, University of Bristol, Bristol, UK.

Ab Schaap (A)

Zambart, School of Medicine, University of Zambia, Lusaka, Zambia.

Peter Godfrey-Faussett (P)

UNAIDS, Geneva, Switzerland.
Clinical Research Department, London School of Hygiene and Tropical Medicine, London, UK.

Helen Ayles (H)

Zambart, School of Medicine, University of Zambia, Lusaka, Zambia.
Clinical Research Department, London School of Hygiene and Tropical Medicine, London, UK.

Sian Floyd (S)

Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.

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