Blood or Urine IP-10 Cannot Discriminate between Active Tuberculosis and Respiratory Diseases Different from Tuberculosis in Children

Abstract

Objectives: Interferon-γ inducible protein 10 (IP-10), either in blood or in urine, has been proposed as a tuberculosis (TB) biomarker for adults. This study aims to evaluate the potential of IP-10 diagnostics in children from Uganda, a high TB-endemic country.

Methods: IP-10 was measured in the blood and urine concomitantly taken from children who were prospectively enrolled with suspected active TB, with or without HIV infection. Clinical/microbiological parameters and commercially available TB-immune assays (tuberculin skin test (TST) and QuantiFERON TB-Gold In-Tube (QFT-IT)) were concomitantly evaluated.

Results: One hundred twenty-eight children were prospectively enrolled. The analysis was performed on 111 children: 80 (72%) of them were HIV-uninfected and 31 (27.9%) were HIV-infected. Thirty-three healthy adult donors (HAD) were included as controls. The data showed that IP-10 is detectable in the urine and blood of children with active TB, independent of HIV status and age. However, although IP-10 levels were higher in active TB children compared to HAD, the accuracy of identifying "active TB" was low and similar to the TST and QFT-IT.

Conclusion: IP-10 levels are higher in children with respiratory illness compared to controls, independent of "TB status" suggesting that the evaluation of this parameter can be used as an inflammatory marker more than a TB test.

Figure 1

Flow chart of the study participants evaluated.

Figure 2

Blood and urine IP-10 levels are significantly increased in children with “active TB” compared to healthy adult donors (HAD). (a-b) Blood IP-10 levels were significantly increased in the children with a diagnosis of “active TB” and “respiratory diseases” compared to HAD, independent of HIV status. (c-d) Urine IP-10 levels were increased in the children diagnosed with “active TB” compared to the other two groups (HAD and “respiratory diseases”). IP-10 ELISA was performed in plasma and urine, and urine IP-10 was normalized with the creatinuria levels. The horizontal lines represent the median; statistical analysis was performed using the Mann-Whitney test with Bonferroni correction and p value was considered significant if <0.016. IP-10: IFN-γ inducible protein 10; HAD: healthy adult donors; TB: tuberculosis; HIV: Human Immunodeficiency Virus.

Figure 3

Blood and urine IP-10 do not correlate with age in children. (a) Spearman rank correlation (r _s) of blood IP-10 and age of children (p = 0.1, r _s = −0.1). (b) Spearman rank correlation (r _s) of urine IP-10 and age in children (p = 0.8, r _s = −0.01). ELISA was performed in blood or urine and urine IP-10 was normalized with the creatinuria levels. Statistical analysis was performed using the Spearman rank correlation test and p value was considered significant if <0.05. IP-10: IFN-γ inducible protein 10.