Specimen Pooling as a Diagnostic Strategy for Microbiologic Confirmation in Children with Intrathoracic Tuberculosis

Walters, Elisabetta; Zalm, Marieke M. van der; Demers, Anne-Marie; Whitelaw, Andrew; Palmer, Megan; Bosch, Corné; Draper, Heather R.; Schaaf, H. Simon; Goussard, Pierre; Lombard, Carl; Gie, Robert P.; Hesseling, Anneke C.

doi:10.1097/inf.0000000000002240

Cited by 17 publications

(21 citation statements)

References 10 publications

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“…Finally, we tested each sample separately so as to investigate the yield from each sample; additional studies using a single Ultra test on combined samples are needed. However, a recent study reported that pooling specimens (IS, gastric lavage, NPA) did not result in improved diagnostic accuracy from Xpert or culture compared with a single specimen (21).…”

Section: Rifampicin Resistance and Time To Resultsmentioning

confidence: 95%

Tuberculosis Diagnosis in Children Using Xpert Ultra on Different Respiratory Specimens

Zar

Workman

Prins

et al. 2019

Am J Respir Crit Care Med

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Rationale: Microbiological confirmation of pulmonary tuberculosis in children is desirable.Objectives: 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.Methods: Consecutive South African children hospitalized with suspected pulmonary tuberculosis were enrolled.Measurements and Main Results: 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 confirmed, unconfirmed, or unlikely 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%) cultureconfirmed 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.Conclusions: 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.

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Section: Rifampicin Resistance and Time To Resultsmentioning

confidence: 95%

Tuberculosis Diagnosis in Children Using Xpert Ultra on Different Respiratory Specimens

Zar

Workman

Prins

et al. 2019

Am J Respir Crit Care Med

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“…For instance, a metaanalysis by Chew and colleagues showed that the collection of a single pooled sample over 24 hours increased the diagnostic yield compared to 'spot' or early morning sputum collection (Chew et al, 2019). Alternative methods such as pooling two induced sputum specimens from the same patient (Mpagama et al, 2012) or continuous overnight collection of sputum (Murphy et al, 2017) have shown utility in increasing the diagnostic yield, although this was not demonstrated in children (Walters et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Use of GeneXpert MTB/RIF on a single pooled sputum specimen to exclude pulmonary tuberculosis among hospital inpatients placed in respiratory isolation

Yeong

Byrne

Cho

et al. 2020

International Journal of Infectious Diseases

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Background: Patients with suspected pulmonary tuberculosis (PTB) are usually placed in respiratory isolation awaiting three sputum smear microscopy results for acid-fast bacilli (3AFB). GeneXpert MTB/ RIF (Xpert) on a pooled sample from two sputa may allow for more rapid de-isolation. Objectives: To compare the sensitivity and negative predictive value (NPV) of Xpert performed on a single pooled sputum sample ('pooled Xpert') to 3AFB, in order to exclude PTB in patients placed in respiratory isolation. Methods: Hospital inpatients in respiratory isolation for possible PTB were enrolled prospectively. Three expectorated sputum samples were obtained for smear microscopy. Two of the same samples had 0.5 ml removed from each and pooled for pooled Xpert. The diagnostic accuracy of pooled Xpert and 3AFB were assessed and compared to liquid culture at 8 weeks as the reference standard. Results: Of 56 participants, nine (16.1%) were diagnosed with PTB. Compared to liquid culture, pooled Xpert had a sensitivity of 88.9% (95% confidence interval (CI) 57-99%) and NPV of 97.9% (95% CI 89-99%). 3AFB had a sensitivity of 66.7% (95% CI 35-88%) and NPV of 93.5% (95% CI 83-98%). Conclusions: A single pooled Xpert was non-inferior to 3AFB, with a strong trend towards greater sensitivity and better NPV. These findings support the use of a single pooled Xpert as an effective rapid screening approach for ruling out PTB in low incidence settings. Its value in high incidence settings and optimal combination with smear microscopy and culture warrant further evaluation.

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“…This demonstrates the difficult clinical dilemma in resource-limited settings, and we would argue that access to even a single Ultra test would be a great step forward to assist clinicians in their clinical judgment and management. It also indicates the importance of identifying the method with the highest yield/cost ratio and the need to consider approaches such as pooled specimen testing that may increase the diagnostic yield from a single test or allow multiple respiratory specimens to be tested with one Ultra cartridge (5, 6).…”

mentioning

confidence: 99%

“…Various respiratory specimen types can be collected, such as gastric aspirates (GA), IS and NPAs, and each have their own advantages and disadvantages. NPA may be easier to obtain, but culture and genotypic yields are lower compared with IS or GA (3, 6). IS and GA are more invasive, but diagnostic yields are higher (3, 6), and in considering the optimal combination of specimens, clinicians need to consider cultural or other barriers to obtain specimens in addition to their combined diagnostic yield (7).…”

mentioning

confidence: 99%

“…NPA may be easier to obtain, but culture and genotypic yields are lower compared with IS or GA (3, 6). IS and GA are more invasive, but diagnostic yields are higher (3, 6), and in considering the optimal combination of specimens, clinicians need to consider cultural or other barriers to obtain specimens in addition to their combined diagnostic yield (7). We need data on Ultra’s performance using GA specimens, as it has demonstrated a better bacteriological yield than IS in one study (6), and single or pooled GA and IS specimens may provide the best yield.…”

mentioning

confidence: 99%

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The Role of Xpert MTB/RIF Ultra in Diagnosing Pulmonary Tuberculosis in Children

Schaaf

Marais

2019

Am J Respir Crit Care Med

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Specimen Pooling as a Diagnostic Strategy for Microbiologic Confirmation in Children with Intrathoracic Tuberculosis

Cited by 17 publications

References 10 publications

Tuberculosis Diagnosis in Children Using Xpert Ultra on Different Respiratory Specimens

Tuberculosis Diagnosis in Children Using Xpert Ultra on Different Respiratory Specimens

Use of GeneXpert MTB/RIF on a single pooled sputum specimen to exclude pulmonary tuberculosis among hospital inpatients placed in respiratory isolation

The Role of Xpert MTB/RIF Ultra in Diagnosing Pulmonary Tuberculosis in Children

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