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Evaluation of the prognostic value of IFN-gamma release assay and tuberculin skin test in household contacts of infectious tuberculosis cases in Senegal.

Lienhardt C, Fielding K, Hane AA, Niang A, Ndao CT, Karam F, Fletcher H, Mbow F, Gomis JF, Diadhiou R, Diadhiou R, Toupane M, Dieye T, Mboup S - PLoS ONE (2010)

Bottom Line: In univariable analysis, the presence of positive TST (> or = 10 mm) and ELISPOT (>32 SFC/million PBMC) responses at baseline were associated with active TB during follow-up: Rate Ratio [RR] = 2.32 (95%CI:1.12-4.84) and RR = 2.09 (95%CI:0.83-5.31), respectively.The median ELISPOT response in contacts who developed TB was 5-fold greater than in those who did not develop TB (p = 0.02).In a TB endemic area, a high ELISPOT response may reflect increased bacterial replication that may subsequently be associated with development of TB disease and may have a prognostic value.

View Article: PubMed Central - PubMed

Affiliation: Institut de Recherche pour le Développement, Programme Tuberculose, Dakar, Senegal. lienhardtc@who.int

ABSTRACT

Background: Chemoprophylaxis of contacts of infectious tuberculosis (TB) cases is recommended for TB control, particularly in endemic countries, but is hampered by the difficulty to diagnose latent TB infection (LTBI), classically assessed through response to the Tuberculin Skin Test (TST). Interferon-gamma release assays (IGRA) are proposed new tools to diagnose LTBI, but there are limited data on their ability to predict the development of active TB disease. To address this, we investigated the response to TST and IGRA in household contacts of infectious TB cases in a TB high-burden country and the potential correlation with development of TB.

Methodology/principal findings: Prospective household contacts study conducted in two health centres in Dakar, Senegal. A total of 2679 household contacts of 206 newly detected smear and/or culture positive index TB cases aged 18 years or greater were identified A TST was performed in each contact and an ESAT6/CFP10 ELISPOT assay performed in a random sample of those. Contacts were followed-up for 24 months. TB was diagnosed in 52 contacts, an incidence rate of 9.27/1000 person-years. In univariable analysis, the presence of positive TST (> or = 10 mm) and ELISPOT (>32 SFC/million PBMC) responses at baseline were associated with active TB during follow-up: Rate Ratio [RR] = 2.32 (95%CI:1.12-4.84) and RR = 2.09 (95%CI:0.83-5.31), respectively. After adjustment for age, sex and proximity to index case, adjusted RRs were 1.51 (95%CI:0.71-3.19) and 1.98 (95%CI:0.77-5.09), respectively. Restricting analysis to the 40 microbiologically confirmed cases, the adjusted RR for positive ELISPOT was 3.61 (95%CI:1.03-12.65). The median ELISPOT response in contacts who developed TB was 5-fold greater than in those who did not develop TB (p = 0.02).

Conclusions/significance: TST and IGRAs are markers of a contact of the immune system with tubercle bacilli. In a TB endemic area, a high ELISPOT response may reflect increased bacterial replication that may subsequently be associated with development of TB disease and may have a prognostic value. Further longitudinal data are needed to assess whether IGRAs are reliable markers to be used for targeting chemoprophylaxis.

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Related in: MedlinePlus

Box plots of EC ELISPOT response (SFC/million PBMC) at baseline by TB status in follow-up.
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pone-0010508-g002: Box plots of EC ELISPOT response (SFC/million PBMC) at baseline by TB status in follow-up.

Mentions: Quantitatively, the median ELISPOT response at baseline in household members who developed TB in follow-up was 250 vs. 50 SFC/106 PBMC in those who did not develop TB (Wilcoxon rank-sum test, p = 0.02) (Fig. 2). Among household members with a positive ELISPOT response (≥32 SFC/106 PBMC - n = 554), those with active TB in follow-up had a higher median response than those without TB (312.5 versus 185 SFC/106 PBMC, respectively; p = 0.06).


Evaluation of the prognostic value of IFN-gamma release assay and tuberculin skin test in household contacts of infectious tuberculosis cases in Senegal.

Lienhardt C, Fielding K, Hane AA, Niang A, Ndao CT, Karam F, Fletcher H, Mbow F, Gomis JF, Diadhiou R, Diadhiou R, Toupane M, Dieye T, Mboup S - PLoS ONE (2010)

Box plots of EC ELISPOT response (SFC/million PBMC) at baseline by TB status in follow-up.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2865542&req=5

pone-0010508-g002: Box plots of EC ELISPOT response (SFC/million PBMC) at baseline by TB status in follow-up.
Mentions: Quantitatively, the median ELISPOT response at baseline in household members who developed TB in follow-up was 250 vs. 50 SFC/106 PBMC in those who did not develop TB (Wilcoxon rank-sum test, p = 0.02) (Fig. 2). Among household members with a positive ELISPOT response (≥32 SFC/106 PBMC - n = 554), those with active TB in follow-up had a higher median response than those without TB (312.5 versus 185 SFC/106 PBMC, respectively; p = 0.06).

Bottom Line: In univariable analysis, the presence of positive TST (> or = 10 mm) and ELISPOT (>32 SFC/million PBMC) responses at baseline were associated with active TB during follow-up: Rate Ratio [RR] = 2.32 (95%CI:1.12-4.84) and RR = 2.09 (95%CI:0.83-5.31), respectively.The median ELISPOT response in contacts who developed TB was 5-fold greater than in those who did not develop TB (p = 0.02).In a TB endemic area, a high ELISPOT response may reflect increased bacterial replication that may subsequently be associated with development of TB disease and may have a prognostic value.

View Article: PubMed Central - PubMed

Affiliation: Institut de Recherche pour le Développement, Programme Tuberculose, Dakar, Senegal. lienhardtc@who.int

ABSTRACT

Background: Chemoprophylaxis of contacts of infectious tuberculosis (TB) cases is recommended for TB control, particularly in endemic countries, but is hampered by the difficulty to diagnose latent TB infection (LTBI), classically assessed through response to the Tuberculin Skin Test (TST). Interferon-gamma release assays (IGRA) are proposed new tools to diagnose LTBI, but there are limited data on their ability to predict the development of active TB disease. To address this, we investigated the response to TST and IGRA in household contacts of infectious TB cases in a TB high-burden country and the potential correlation with development of TB.

Methodology/principal findings: Prospective household contacts study conducted in two health centres in Dakar, Senegal. A total of 2679 household contacts of 206 newly detected smear and/or culture positive index TB cases aged 18 years or greater were identified A TST was performed in each contact and an ESAT6/CFP10 ELISPOT assay performed in a random sample of those. Contacts were followed-up for 24 months. TB was diagnosed in 52 contacts, an incidence rate of 9.27/1000 person-years. In univariable analysis, the presence of positive TST (> or = 10 mm) and ELISPOT (>32 SFC/million PBMC) responses at baseline were associated with active TB during follow-up: Rate Ratio [RR] = 2.32 (95%CI:1.12-4.84) and RR = 2.09 (95%CI:0.83-5.31), respectively. After adjustment for age, sex and proximity to index case, adjusted RRs were 1.51 (95%CI:0.71-3.19) and 1.98 (95%CI:0.77-5.09), respectively. Restricting analysis to the 40 microbiologically confirmed cases, the adjusted RR for positive ELISPOT was 3.61 (95%CI:1.03-12.65). The median ELISPOT response in contacts who developed TB was 5-fold greater than in those who did not develop TB (p = 0.02).

Conclusions/significance: TST and IGRAs are markers of a contact of the immune system with tubercle bacilli. In a TB endemic area, a high ELISPOT response may reflect increased bacterial replication that may subsequently be associated with development of TB disease and may have a prognostic value. Further longitudinal data are needed to assess whether IGRAs are reliable markers to be used for targeting chemoprophylaxis.

Show MeSH
Related in: MedlinePlus