Tuberculosis Diagnosis in Children Using Xpert Ultra on Different Respiratory Specimens.

Abstract

<b>Rationale:</b> Microbiological confirmation of pulmonary tuberculosis in children is desirable.<b>Objectives:</b> To investigate the diagnostic accuracy and incremental yield of Xpert MTB/RIF Ultra (Ultra; Cepheid), a new rapid test, on repeated induced sputum, nasopharyngeal aspirates, and combinations of specimens.<b>Methods:</b> Consecutive South African children hospitalized with suspected pulmonary tuberculosis were enrolled.<b>Measurements and Main Results:</b> Induced sputum (IS) and nasopharyngeal aspirates (NPAs) were obtained. NPAs were frozen; IS underwent liquid culture, and an aliquot was frozen. Ultra was performed on thawed NPAs and IS specimens individually. Children were categorized as <i>confirmed, unconfirmed</i>, or <i>unlikely</i> tuberculosis according to NIH consensus case definitions. The diagnostic accuracy of Ultra was compared with liquid culture on IS. In total, 195 children (median age: 23.3 mo; 32 [16.4%] HIV-infected) had one IS and NPA, and 130 had two NPAs. There were 40 (20.5%) culture-confirmed cases. Ultra was positive on NPAs in 26 (13.3%) and on IS in 31 (15.9%). Sensitivity and specificity of Ultra on one NPA were 46% and 98%, respectively, and similar by HIV status. Sensitivity and specificity of Ultra on one IS were 74.3% and 96.9% respectively. Combining one NPA and one IS increased sensitivity to 80%. Sensitivity using Ultra on two NPAs was 54.2%, increasing to 87.5% with an IS Ultra.<b>Conclusions:</b> IS provides a better specimen than repeated NPA for rapid diagnosis using Ultra. However, Ultra testing of combinations of specimens provides a novel strategy that can be adapted to identify most children with confirmed pulmonary tuberculosis.