Evaluation of Xpert MTB/RIF and MODS assay for the diagnosis of pediatric tuberculosis

Abstract

BackgroundTuberculosis (TB) in children is rarely confirmed due to the lack of effective diagnostic tools; only 10 to 15% of pediatric TB is smear positive due to paucibacillary samples and the difficulty of obtaining high-quality specimens from children. We evaluate here the accuracy of Xpert MTB/RIF in comparison with the Micoroscopic observation drug susceptibility (MODS) assay for diagnosis of TB in children using samples stored during a previously reported evaluation of the MODS assay.MethodsNinety-six eligible children presenting with suspected TB were recruited consecutively at Pham Ngoc Thach Hospital in Ho Chi Minh City Viet Nam between May to December 2008 and tested by Ziehl-Neelsen smear, MODS and Mycobacterial growth Indicator (MGIT, Becton Dickinson) culture. All samples sent by the treating clinician for testing were included in the analysis. An aliquot of processed sample deposit was stored at −20°C and tested in the present study by Xpert MTB/RIF test. 183 samples from 73 children were available for analysis by Xpert. Accuracy measures of MODS and Xpert were summarized.ResultsThe sensitivity (%) in detecting children with a clinical diagnosis of TB for smear, MODS and Xpert were 37.9 [95% CI 25.5; 51.6], 51.7 [38.2; 65.0] and 50.0 [36.6; 63.4], respectively (per patient analysis). Xpert was significantly more sensitive than smear (P=0.046). Testing of additional samples did not increase case detection for MODS while testing of a second sputum sample by Xpert detected only two additional cases. The positive and negative predictive values (%) of Xpert were 100.0 [88.0; 100.0] and 34.1 [20.5; 49.9], respectively, while those of MODS were 96.8 [83.3; 99.9] and 33.3 [19.6; 49.5].ConclusionMODS culture and Xpert MTB/RIF test have similar sensitivities for the detection of pediatric TB. Xpert MTB RIF is able to detect tuberculosis and rifampicin resistance within two hours. MODS allows isolation of cultures for further drug susceptibility testing but requires approximately one week to become positive. Testing of multiple samples by xpert detected only two additional cases and the benefits must be considered against costs in each setting. Further research is required to evaluate the optimal integration of Xpert into pediatric testing algorithms.

Xpert MTB/RIF® como herramienta diagnóstica en una cohorte de niños menores de 15 años con sospecha clínica de tuberculosis pulmonar en un hospital de alta complejidad de Medellín

“…En diferentes estudios realizados en niños, la sensibilidad de Xpert MTB/RIF en EI con baciloscopia positiva varía de 92 a 100% [24][25][26] y cuando se emplean muestras de jugo gástrico, la sensibilidad se estima entre 64 y 95% 8,27,28 . En nuestro caso el único paciente con baciloscopia positiva también presentó resultado positivo de la prueba molecular en EI, con una sensibilidad del 100%.…”

Childhood Tuberculosis

“…[50] has concluded that this test will not be a crucial diagnostic tool in high burden countries, the WHO endorsed its use in children in 2013. Several studies published on its use in the pediatric population have shown promising results be it in gastric lavage [51,52], sputum [53][54][55][56][57][58][59], bronchoalveolar lavage specimens [60], or stool in HIV-infected patients [61].…”

What steps do we need to take to improve diagnosis of tuberculosis in children?

“…Liquid methods are based on two characteristics of M. tuberculosis: its faster growth and its distinctive morphology in liquid media. Recently, another liquid culture-based method, known as microscopic observation drug susceptibility (MODS), has been evaluated in three studies done in Vietnam, respectively, on 705, 96 and 73 children, including overall 1524 pediatric samples [62][63][64]. In the first study, MODS sensitivity was compared with Lowenstein-Jensen culture, resulting higher considering both by patients and by samples (46 vs 38.9%; 35.3 vs 30.3%; p < 0.001) [62].…”