Xpert MTB/RIF and Xpert MTB/RIF Ultra assays for active tuberculosis and rifampicin resistance in children

Kay, Alexander; Fernández, Lucía; Takwoingi, Yemisi; Eisenhut, Michael; Detjen, Anne; Steingart, Karen R; Mandalakas, Anna M.

doi:10.1002/14651858.cd013359.pub2

Cited by 60 publications

(45 citation statements)

References 178 publications

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“…However, especially for younger children, comparisons between paediatric and adult pulmonary tuberculosis are challenging because the diseases are so di erent. One Cochrane Review of Xpert MTB/RIF diagnostic accuracy for childhood tuberculosis reported accuracy estimates that were similar to the estimates in this review for Xpert MTB/RIF used in a screening context (Kay 2020). However, our findings for Xpert MTB/RIF accuracy were limited as the numbers of studies and participants enrolled were small.…”

Section: Comparison With Other Systematic Reviewssupporting

confidence: 68%

“…Another consideration for comparisons against the microbiological reference standard is variation between number of specimens tested for a particular individual, with multiple specimen testing likely increasing the yield of the reference standard (Cruz 2012;Zar 2012), and thereby influencing accuracy estimates of the index test. Accuracy of microbiological testing for pulmonary childhood tuberculosis also varies by the type of specimen collected, with invasively collected specimens, such as gastric aspirates, typically more accurate in younger children (Dunn 2016;Kay 2020). Given the limited data available for this review against a microbiological reference standard, we did not investigate the number of specimens tested or type of specimen.…”

Section: Accuracy Of the Reference Standards Usedmentioning

confidence: 99%

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Screening tests for active pulmonary tuberculosis in children

Vonasek

Ness

Takwoingi

et al. 2021

Cochrane Database of Systematic Reviews

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Background Globally, children under 15 years represent approximately 12% of new tuberculosis cases, but 16% of the estimated 1.4 million deaths. This higher share of mortality highlights the urgent need to develop strategies to improve case detection in this age group and identify children without tuberculosis disease who should be considered for tuberculosis preventive treatment. One such strategy is systematic screening for tuberculosis in high‐risk groups. Objectives To estimate the sensitivity and specificity of the presence of one or more tuberculosis symptoms, or symptom combinations; chest radiography (CXR); Xpert MTB/RIF; Xpert Ultra; and combinations of these as screening tests for detecting active pulmonary childhood tuberculosis in the following groups. – Tuberculosis contacts, including household contacts, school contacts, and other close contacts of a person with infectious tuberculosis. – Children living with HIV. – Children with pneumonia. – Other risk groups (e.g. children with a history of previous tuberculosis, malnourished children). – Children in the general population in high tuberculosis burden settings. Search methods We searched six databases, including the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase, on 14 February 2020 without language restrictions and contacted researchers in the field. Selection criteria Cross‐sectional and cohort studies where at least 75% of children were aged under 15 years. Studies were eligible if conducted for screening rather than diagnosing tuberculosis. Reference standards were microbiological (MRS) and composite reference standard (CRS), which may incorporate symptoms and CXR. Data collection and analysis Two review authors independently extracted data and assessed study quality using QUADAS‐2. We consolidated symptom screens across included studies into groups that used similar combinations of symptoms as follows: one or more of cough, fever, or poor weight gain and one or more of cough, fever, or decreased playfulness. For combination of symptoms, a positive screen was the presence of one or more than one symptom. We used a bivariate model to estimate pooled sensitivity and specificity with 95% confidence intervals (CIs) and performed analyses separately by reference standard. We assessed certainty of evidence using GRADE. Main results Nineteen studies assessed the following screens: one symptom (15 studies, 10,097 participants); combinations of symptoms (12 studies, 29,889 participants); CXR (10 studies, 7146 participants); and Xpert MTB/RIF (2 studies, 787 participants). Several studies assessed more than one screening test. No studies assessed Xpert Ultra. For 16 studies (84%), risk of bias for the reference standard domain was unclear owing to concern about incorporation bias...

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Section: Comparison With Other Systematic Reviewssupporting

confidence: 68%

Section: Accuracy Of the Reference Standards Usedmentioning

confidence: 99%

Screening tests for active pulmonary tuberculosis in children

Vonasek

Ness

Takwoingi

et al. 2021

Cochrane Database of Systematic Reviews

Self Cite

View full text Add to dashboard Cite

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“…Disease often manifests as pauci-bacillary and can be either pulmonary or extra-pulmonary disease ( Piccini et al., 2014 ; Highsmith et al., 2019 ). In addition, children tend to swallow respiratory secretions necessitating other uncomfortable procedures such as gastric lavage or sputum induction ( Velayati, 2016 ; Kay et al., 2020 ). There is therefore an urgent need to improve TB diagnosis in children and/or to develop improved diagnostic tools, together with actively exploring the testing of new, non-invasive specimen types.…”

Section: Discussionmentioning

confidence: 99%

Detection of Mycobacterium tuberculosis Complex Bacilli and Nucleic Acids From Tongue Swabs in Young, Hospitalized Children

Ealand

Peters

Jacobs

et al. 2021

Front. Cell. Infect. Microbiol.

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Diagnosis of tuberculosis in pediatric patients remains challenging due to inherent difficulties associated with obtaining respiratory samples for molecular and culture-based testing. To address this, recent studies have highlighted the utility of tongue swabs to detect Mycobacterium tuberculosis genomic DNA in the oral epithelia of tuberculosis infected adults. It is unknown whether tongue swabs have similar utility for diagnosis of childhood tuberculosis and if the presence of DNA in these swabs was associated with whole bacilli. We therefore sought to conduct a preliminary assessment of the utility of tongue swabs to detect tubercle bacilli and their associated genetic material in young children. For this, we recruited hospitalized children with clinically diagnosed tuberculosis (n = 26) or lower respiratory tract infection (LRTI, n = 9). These categories were blinded for downstream laboratory tests, which included PCR, spoligotyping, smear microscopy, and culture. Mtb genomic DNA was detected by PCR only in clinically diagnosed TB cases [11/26 (31.4%)] and not in cases with LRTI. Of these, 5/11 [45.5%] were associated with a spoligotype. Spoligotyping also detected an additional six specimens that were negative by PCR. Using smear microscopy, 19/26 [73.1%] and 4/9 [44.4] were Mtb positive in the tuberculosis or LRTI categories respectively. We noted positive results on all three tests in 5/26 [19.2%] in the tuberculosis category and 0/9 in the LRTI category. All specimens were culture negative. Collectively, these preliminary data present a compelling case for broader testing of tongue swabs to diagnose tuberculosis in children where obtaining standard sputum specimens is not easy.

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“…Cochrane review by Kay et al concluded higher sensitivity in gastric aspirate samples followed by sputum stool, and nasopharyngesl aspirate, while the specificity was >98%. Genexpert Ultra had higher sensitivity but lower specificity than Xpert in data from 299 studies ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

Childhood Intra-Thoracic Tuberculosis Clinical Presentation Determines Yield of Laboratory Diagnostic Assays

et al. 2021

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Diagnosis of intra-thoracic tuberculosis (ITTB) in children is difficult due to the paucibacillary nature of the disease, the challenge in collecting appropriate specimens, and the low sensitivity of smear microscopy and culture. Culture and Xpert MTB/RIF provide higher diagnostic yield in presumptive TB in adults than in children. Current study was designed to understand poor yield of diagnostic assays in children. Children with presumptive ITTB were subjected to gastric aspirates and induced sputum twice. Samples were tested by Ziehl-Neelsen stain, Xpert MTB/RIF-assay, and MGIT-960 culture. Subjects were grouped as Confirmed, Unconfirmed, and Unlikely TB, and classified as progressive primary disease (PPD, lung parenchymal lesion), and primary pulmonary complex (PPC, hilar lymphadenopathy) on chest X-ray. Of children with culture-positive TB 51/394 (12.9%), culture-negative TB 305 (77.4%), and unlikely TB 38 (9.6%), 9 (2.3%) were smear positive, while 95 (24.1%) were Xpert-MTB/RIF positive. Xpert-MTB/RIF detected 40/51 culture confirmed cases (sensitivity 78.4% and NPV 96.3%). Culture was positive in more children presenting as PPD (p < 0.04). In culture-negative TB group, Xpert positivity was seen in 31% of those with PPD and 11.9% in those with PPC (p < 0.001).Conclusion: Xpert-MTB/RIF improved diagnosis by 2-fold and increased detection of MDR-TB. Both liquid culture and Xpert-MTB/RIF gave higher yield in children with lung parenchymal lesions. Children with hilar lymphadenopathy without active lung parenchymal lesions had poor diagnostic yield even with sensitive nucleic acid amplification tests, due to paucibacillary/localized disease, suggesting possible utility of invasively collected samples in early diagnosis and treatment.

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Xpert MTB/RIF and Xpert MTB/RIF Ultra assays for active tuberculosis and rifampicin resistance in children

Cited by 60 publications

References 178 publications

Screening tests for active pulmonary tuberculosis in children

Screening tests for active pulmonary tuberculosis in children

Detection of Mycobacterium tuberculosis Complex Bacilli and Nucleic Acids From Tongue Swabs in Young, Hospitalized Children

Childhood Intra-Thoracic Tuberculosis Clinical Presentation Determines Yield of Laboratory Diagnostic Assays

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