The Use of Interferon Gamma Inducible Protein 10 as a Potential Biomarker in the Diagnosis of Latent Tuberculosis Infection in Uganda (original) (raw)
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The Pediatric Infectious Disease Journal, 2008
Background: Children in contact with adults with pulmonary tuberculosis (TB) are at risk for infection and disease progression, and chemoprophylaxis may reduce this risk. The identification of infection is based on the tuberculin skin test (TST) and interferon-␥ (INF-␥) release assays. Other biomarkers such as interferon-␥induced-protein 10 (IP-10) may have potential for the diagnosis of latent TB infections. Objectives: To describe IP-10 concentrations and their association to TST and INF-␥ responses in children recently exposed to adults with smear-positive TB in Brazil and Nepal. Methods: Two surveys using the same design were undertaken to describe TST, INF-␥, and IP-10 responses in 146 children in Nepal and 113 children in Brazil. Results: The concordance of TST and QuantiFERON-TB gold in-tube (QFT-IT) was high ( 0.73 in Brazil and 0.80 in Nepal). IP-10 responses were higher in children with both positive TST and positive QFT-IT (medians 1434 pg/mL in Brazil and 1402 pg/mL in Nepal) and lowest in children with both negative TST and negative QFT-IT (medians 206 pg/mL in Brazil and 81 pg/mL in Nepal). Children with negative TST and positive QFT-IT had higher IP-10 concentrations than children with positive TST but negative QFT-IT. Conclusions: IP-10 is a potential marker to identify latent TB infections that is expressed in large quantities and with good agreement with QFT-IT. The reasons for the discrepant results observed are discussed.
BioMed Research International, 2015
Objectives. Interferon-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 HIVuninfected 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.
European Respiratory Journal, 2010
In patients latently infected with Mycobacterium tuberculosis, immunosuppression significantly augments the risk of progression to active tuberculosis (TB) and TB is still one of the most frequent opportunistic infections worldwide. Prevention of TB in HIV-positive patients using the tuberculin skin testing (TST) followed by targeted preventive treatment is an effective strategy, but has thus far shown limited clinical success, in part due to the lack of a reliable test for latent TB infection (LTBI) [1]. Interferon (IFN)-c release assays (IGRAs) have shown great potential in the improvement of LTBI diagnosis, but the tests perform suboptimally in immunocompromised populations. We and others have previously shown that HIV-positive patients have high rates of indeterminate QuantiFERON1-TB Gold In-Tube test (QFT-IT) results and that this, at least in part, is due to low CD4 T-cell count [2-4].
Advances in Infectious Diseases
Background: The diagnosis and treatment of active tuberculosis and the detection/management of latent tuberculosis infection (LTBI) cases are the two main strategies for the TB control, particularly in endemic countries. Tuberculin skin test (TST) and Interferon Gamma Release Assays (IGRAs) are tools for detection of LTBI. The objective of this study was to evaluate the performance of the TST and QuantiFERON-TB Gold Plus ® (QTF-Plus) and to identify a threshold for TST in best agreement with QTF-Plus for LTBI detection in a high TB burden setting. Methods: In July 2020, a cross-sectional analytical study was performed for QFT-Plus using blood samples and TST in 101 individuals with a high risk of TB living in Bobo-Dioulasso, Burkina Faso. A crude comparison between both tests was done and receiver operating characteristic curve was generated to determine TST's threshold.
Is IP-10 an Accurate Marker for Detecting M. tuberculosis-Specific Response in HIV-Infected Persons?
PLoS ONE, 2010
Background: The suboptimal sensitivity of Interferon (IFN)-c-based in-vitro assays, especially in immunocompromised individuals, emphasizes the need for alternative markers for diagnosing tuberculosis (TB). The objective of this study was to evaluate whether interferon-inducible protein (IP)-10, monocyte chemotactic protein (MCP)-2 and interleukin (IL)-2 can be useful biomarkers for evaluating a specific response to RD1 antigens associated to active TB disease in HIV-infected individuals.
The American journal of tropical medicine and hygiene, 2016
Interferon-gamma (IFN-γ) release assays (IGRAs) are used to detect cellular immune recognition of Mycobacterium tuberculosis. The chemokine IFN-γ-inducible protein 10 (IP-10) is an alternative diagnostic biomarker to IFN-γ. Several conditions interfere with IGRA test performance. We aimed to assess the possible influence of Plasmodium falciparum infection on the IGRA test QuantiFERON-TB GOLD(®) In-Tube (QFT) test and an in-house IP-10 release assay. In total, 241 Tanzanian adults were included; 184 patients with uncomplicated malaria (88 human immunodeficiency virus [HIV] coinfected) and 57 HIV-infected patients without malaria infection. Malaria was treated with artemether-lumefantrine (Coartem(®)). QFT testing was performed before initiation of malaria treatment and at days 7 and 42. In total, 172 patients completed follow-up. IFN-γ and IP-10 was measured in QFT supernatants. We found that during malaria infection IFN-γ and IP-10 levels in the unstimulated samples were elevated, m...
2013
Background: Diagnosis of childhood tuberculosis is challenging. The widely used tuberculin skin test has many limitations. In this study, we evaluated the role of QuantiFERON-Gold-In-Tube (QFT-IT) and Interferon gamma inducible protein 10 (IP-10) for diagnosis of active TB. We further studied their efficacy in monitoring the effect of anti-tuberculous therapy. Methods: The study comprised two population groups. Group I comprised 53 children and adolescents diagnosed with active TB, whereas Group II comprised 33 patients recruited at different time intervals: at 2, 4, and 6 months following start of treatment. Blood samples were withdrawn from each patient for measurement of interferon-gamma (IFN-γ) and IP-10 levels. Statistical package SPSS version 15.0 for Windows was used for statistical analysis. Results: QFT-IT and IP-10 tests yielded sensitivities of 86% and 86.5%; and specificities of 33% and 44.4% respectively. Combining both tests improved sensitivity to 91.89%. A highly sig...
A major challenge in the global Tuberculosis (TB) control is the diagnosis and treatment of Latent Tuberculosis Infection (LTBI). In the absence of any reference standard test for the diagnosis of LTBI, this study set out to compare the performance of the two current immune-based tests, Tuberculin Skin Test (TST) and Quantiferon–TB Gold In–Tube (QFT-GIT) ELISA in the diagnosis of LTBI. Two sets of diagnostic results for 196 apparently healthy volunteers from a cross-section of Okada Community, Edo State, Nigeria were compared in terms of age, occupation, BCG-vaccination status, prior TST and cigarette smoking history. Overall, 56 (28.6%) and 81 (41.3%) of the subjects were diagnosed with LTBI by the QFT-GIT test and TST respectively. The LTBI prevalence as assessed by the QFT-GIT test was significantly higher among the non-BCG-vaccinated, compared to the BCG-vaccinees (X 2 =18.79, df=1, p=0.0001). The highest concordance (QFT-GIT+ve/TST+ve) was found in the occupation categories (Ʀ=-0.009, p=0.747) and the highest discordance(QFT-GIT –ve/TST +ve) was with respect to the BCG-vaccination status (Ʀ=-0.194, p=0.046).The disparity in the performance of the two tests is attributable to the high false – positive TST results, which is a direct reflection of high (90.8%) BCG vaccination level among the study population. It is advocated that the two-step testing approach, using the QFT-GIT assay as a confirmatory test for LTBI after initial positive screening by the TST, be introduced into the TB control strategy in TB – laden communities with high BCG vaccination coverage.