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      Xpert MTB/RIF Testing of Stool Samples for the Diagnosis of Pulmonary Tuberculosis in Children

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          Abstract

          In a pilot accuracy study, stool Xpert testing from 115 children with suspected pulmonary tuberculosis (PTB) detected 8/17 (47%) cultureconfirmed tuberculosis cases, including 4/5 (80%) HIV-infected and 4/12 (33%) HIV-uninfected children. Sputum Xpert detected 11/17 (65%) cases. Stool holds promise for PTB diagnosis in HIV-infected children.

          Abstract

          In a pilot accuracy study, stool Xpert testing from 115 children with suspected pulmonary tuberculosis (PTB) detected 8/17 (47%) culture-confirmed tuberculosis cases, including 4/5 (80%) HIV-infected and 4/12 (33%) HIV-uninfected children. Sputum Xpert detected 11/17 (65%) cases. Stool holds promise for PTB diagnosis in HIV-infected children.

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          Induced sputum versus gastric lavage for microbiological confirmation of pulmonary tuberculosis in infants and young children: a prospective study.

          For microbiological confirmation of diagnosis of pulmonary tuberculosis in young children, sequential gastric lavages are recommended; sputum induction has not been regarded as feasible or useful. We aimed to compare the yield of Mycobacterium tuberculosis from repeated induced sputum with that from gastric lavage in young children from an area with a high rate of HIV and tuberculosis. We studied 250 children aged 1 month to 5 years who were admitted for suspected pulmonary tuberculosis in Cape Town, South Africa. Sputum induction and gastric lavage were done on three consecutive days according to a standard procedure. Specimens were stained for acid-fast bacilli; each sample was cultured singly for M tuberculosis. Median age of children was 13 months (IQR 6-24). A positive smear or culture for M tuberculosis was obtained from 62 (25%) children; of these, 58 (94%) were positive by culture, whereas almost half (29 [47%]) were smear positive. Samples from induced sputum and gastric lavage were positive in 54 (87%) and 40 (65%) children, respectively (difference in yield 5.6% [1.4-9.8%], p=0.018). The yield from one sample from induced sputum was similar to that from three gastric lavages (p=1.0). Microbiological yield did not differ between HIV-infected and HIV-uninfected children (p=0.17, odds ratio 0.7 [95% CI 0.3-1.3]). All sputum induction procedures were well tolerated; minor side-effects were increased coughing, epistaxis, vomiting, or wheezing. Sputum induction is safe and useful for microbiological confirmation of tuberculosis in young children. This technique is preferable to gastric lavage for diagnosis of pulmonary tuberculosis in both HIV-infected and HIV-uninfected infants and children.
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            Rapid molecular diagnosis of pulmonary tuberculosis in children using nasopharyngeal specimens.

            A rapid diagnosis of pediatric pulmonary tuberculosis (PTB) using Xpert MTB/RIF (Mycobacterium tuberculosis/rifampicin) automated testing on induced sputum (IS) is possible, but the capacity for performing IS is limited. The diagnosis using a nasopharyngeal aspirate (NPA), which can be non-invasively obtained, is desirable. Paired specimens (NPA and IS) were tested using smear, liquid culture and Xpert. The diagnostic accuracy of Xpert and smear was compared with culture for different specimens in children with suspected PTB. There were 535 children [median age 19 months, 117 (21·9%) HIV-infected] who had one IS and one NPA specimen; 396 had two paired specimens. A positive smear, Xpert test or culture occurred in 30 (5.6%), 81 (15.1%) and 87 children (16.3%), respectively. The culture yield was higher from IS (84/87, 96.6%) vs NPA (61/87, 70.1%, P < .001). Amongst children with two paired specimens, 63 culture-confirmed cases occurred [60 (95.2%) IS vs 48 (76.2%) NPA, P = .002]. The sensitivity of two Xpert tests was similar for IS and NPAs [(45/63) 71% vs (41/63) 65%, P = .444)]; the sensitivity of smear was lower for IS (21/63, 33%) and NPA (16/63, 25%). The incremental yield from a second IS was 9 cases (17.6%) by culture and 9 (25%) by Xpert testing; a second NPA increased the culture yield by 10 (26.3%) and Xpert by 11 (36.7%). Xpert specificity was 99.1% (98.1-100) for IS and 98.2% (96.8-99.6) for NPAs. Xpert testing provided faster results than culture (median 0 vs 15 days, P < .001). Xpert testing on 2 NPAs is useful in children with suspected PTB, particularly in settings where IS and culture are not feasible.
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              Assessment of the Xpert MTB/RIF assay for diagnosis of tuberculosis with gastric lavage aspirates in children in sub-Saharan Africa: a prospective descriptive study

              Rapid and accurate diagnosis of pulmonary tuberculosis in children remains challenging because of difficulties in obtaining sputum samples and the paucibacillary nature of the disease. The Xpert MTB/RIF assay is useful for rapid diagnosis of childhood tuberculosis with sputum and nasopharyngeal samples. We assessed this assay for the detection of tuberculosis and multidrug resistant (MDR) tuberculosis with gastric lavage aspirate (GLA) samples in children admitted to hospital. We did a prospective study to assess the sensitivity and specificity of the Xpert MTB/RIF assay with GLA samples for the detection of pulmonary tuberculosis and MDR tuberculosis in new paediatric inpatient admissions at the University Teaching Hospital, Lusaka, Zambia. Children aged 15 years or younger were recruited between June, 2011, and May, 2012. GLA and sputum were analysed by standard smear-microscopy, mycobacterial growth indicator tube (MGIT) culture, MGIT drug-susceptibility testing, and the Xpert MTB/RIF assay. Sensitivity of the Xpert MTB/RIF assay was assessed with the Pearson χ(2) or Fishers exact test. Of 930 children, 142 produced sputum and GLA was obtained from 788 non-sputum producers. Culture-positive tuberculosis was identified in 58 (6·2%) of 930 children: ten from sputum producers and 48 from GLA of non-sputum producers. The sensitivity and specificity of the Xpert MTB/RIF assay were similar: sensitivity was 68·8% (95% CI 53·6-80·9) for GLA versus 90·0% (54·1-99·5; p=0·1649) for sputum samples; specificity was 99·3% (98·3-99·8) for GLA and 98·5% (94·1-99·7; p=0·2871) for sputum samples. The Xpert MTB/RIF assay detected an extra 28 tuberculosis cases compared with smear microscopy and was significantly more sensitive than smear microscopy for both sputum (90·0% [54·1-99·5] vs 30·0% [8·1-64·6], p=0·01) and GLA (68·8% [53·6-80·9] vs 25·0% [14·1-40·0], p<0·0001). The assay load did not differ significantly by sample type (p=0·791). 22 children were infected with HIV and tuberculosis and significant differences in assay performance could not be detected when stratifying by HIV status for either sample type. The Xpert MTB/RIF assay detected rifampicin resistance in three GLA samples: two confirmed as MDR tuberculosis and one false positive. Analyses of GLA samples with the Xpert MTB/RIF assay is a sensitive and specific method for rapid diagnosis of pulmonary tuberculosis in children who cannot produce sputum. The single site nature of our study invites caution. European Commission, European Developing Countries Clinical Trials Partnership, and UBS Optimus Foundation. Copyright © 2013 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Clin Infect Dis
                Clin. Infect. Dis
                cid
                cid
                Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
                Oxford University Press
                1058-4838
                1537-6591
                1 August 2013
                11 April 2013
                11 April 2013
                : 57
                : 3
                : e18-e21
                Affiliations
                [1 ]Division of Medical Microbiology and Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, and National Health Laboratory Service of South Africa, South Africa
                [2 ]Division of Infection and Immunity, University College London, United Kingdom
                [3 ]Department of Paediatrics and Child Health, University of Cape Town
                [4 ]Red Cross WarMemorial Children's Hospital , Cape Town, South Africa
                Author notes
                Correspondence: Mark Nicol, MBBCh, MMed, PhD, 5.28 Falmouth, Faculty of Health Sciences, Anzio Road, Observatory, Cape Town, 7925, South Africa ( mark.nicol@ 123456uct.ac.za ).
                Article
                cit230
                10.1093/cid/cit230
                3703104
                23580738
                71f8e15b-1dc6-4c2c-a50c-73fdd04bb391
                © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 January 2013
                : 1 April 2013
                Categories
                Electronic Article

                Infectious disease & Microbiology
                tuberculosis,children,xpert,stool,diagnosis
                Infectious disease & Microbiology
                tuberculosis, children, xpert, stool, diagnosis

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