Africa-wide evaluation of host biomarkers in QuantiFERON supernatants for the diagnosis of pulmonary tuberculosis.
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Chegou Novel N, Sutherland Jayne S, Namuganga Anna-Ritah, Corstjens Paul Lam, Geluk Annemieke, Gebremichael Gebremedhin, Mendy Joseph, Malherbe Stephanus, Stanley Kim, van der Spuy Gian D, Kriel Magdalena, Loxton Andre G, Kriel Belinda, Simukonda Felanji, Bekele Yonas, Sheehama Jacob A, Nelongo Josefina, van der Vyver Marieta, Gebrexabher Atsbeha, Hailu Habteyes, Esterhuyse Maria M, Rosenkrands Ida, Aagard Claus, Kidd Martin, Kassa Desta, Mihret Adane, Howe Rawleigh, Cliff Jacqueline M, Crampin Amelia C, Mayanja-Kizza Harriet, Kaufmann Stefan H E, Dockrell Hazel M, Ottenhoff Tom H M, Walzl Gerhard, AE-TBC consortium
Аннотация
We investigated host-derived biomarkers that were previously identified in QuantiFERON supernatants, in a large pan-African study. We recruited individuals presenting with symptoms of pulmonary TB at seven peripheral healthcare facilities in six African countries, prior to assessment for TB disease. We then evaluated the concentrations of 12 biomarkers in stored QuantiFERON supernatants using the Luminex platform. Based on laboratory, clinical and radiological findings and a pre-established algorithm, participants were classified as TB disease or other respiratory diseases(ORD). Of the 514 individuals included in the study, 179(34.8%) had TB disease, 274(51.5%) had ORD and 61(11.5%) had an uncertain diagnosis. A biosignature comprising unstimulated IFN-γ, MIP-1β, TGF-α and antigen-specific levels of TGF-α and VEGF, identified on a training sample set (n = 311), validated by diagnosing TB disease in the test set (n = 134) with an AUC of 0.81(95% CI, 0.76-0.86), corresponding to a sensitivity of 64.2%(95% CI, 49.7-76.5%) and specificity of 82.7%(95% CI, 72.4-89.9%). Host biomarkers detected in QuantiFERON supernatants can contribute to the diagnosis of active TB disease amongst people presenting with symptoms requiring investigation for TB disease, regardless of HIV status or ethnicity in Africa.