Xpert MTB/RIF Ultra versus Xpert MTB/RIF for the diagnosis of tuberculous meningitis: a prospective, randomised, diagnostic accuracy study

Donovan, Joseph; Thu, Do Dang Anh; Phu, Nguyen Hoan; Dung, Vu Thi Mong; Quang, Tran Phu; Nghia, Ho Dang Trung; Oanh, Pham Kieu Nguyet; Nhu, Tran Bao; Châu, Nguyễn Văn Vĩnh; Ha, Vu Thi Ngoc; Hang, Vu Thi Ty; Trinh, Dong Huu Khanh; Geskus, Ronald B.; Tan, Le Van; Thuong, Nguyen Thuy Thuong; Thwaites, Guy

doi:10.1016/s1473-3099(19)30649-8

Cited by 101 publications

(83 citation statements)

References 21 publications

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“…Several studies have been published on the diagnostic accuracy of Ultra in extrapulmonary specimens 11,14,15,[17][18][19][20][21][22][23][24][25]28,29 . Most of the studies were performed in TB endemic settings 14,17,[19][20][21][22][23][24][25]28,29 , and only three studies have investigated Ultra test performance in low TB prevalence settings 11,15,18 . However, two of these studies were retrospective and performed on selected sample material.…”

Section: Discussionmentioning

confidence: 99%

“…This is in concordance with the specificities (97-100%) found in other low TB prevalent settings where culture was used as reference standard 15,18 . However, in most of the studies that directly compare the performance of Xpert and Ultra, the specificity of Ultra is reduced compared to Xpert, both in extrapulmonary specimens 14,19,20,22,29 and sputum 9,10,12,13 . In low TB prevalent settings, even a small reduction in specificity could lead to unacceptable high rates of false positive cases, emphasizing that Ultra should be performed on selected samples with a high pre-test probability of TB disease.…”

Section: Discussionmentioning

confidence: 99%

“…Most, but not all 28,29 , of the studies that investigate Ultra for the diagnosis of EPTB suggest increased sensitivity of Ultra compared to Xpert in different extrapulmonary specimens 11,14,15,17,[19][20][21][22][23]25 . When culture is used as reference standard, the reported sensitivity of Ultra varies, but is generally high in lymph node specimens (90-94%) 18,24 , FNAs and tissue samples (87-95%) 18,22 , cerebrospinal fluid (80-100%) 17,18,21,25,29 and pus specimens (65-95%) 18,19 , and lower in pleural fluid samples (48-84%) 18,20,22,23 , which is in line with our findings. Several of the studies also show that Ultra can detect MTC in culture negative specimens from clinically diagnosed TB cases 17,[19][20][21][22][23][24][25]28,29 , thus, contributing to improved diagnosis of TB in samples with a very low bacillary load.…”

Section: Discussionmentioning

confidence: 99%

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Xpert MTB/RIF ultra for rapid diagnosis of extrapulmonary tuberculosis in a high-income low-tuberculosis prevalence setting

Hoel

Syre

Skarstein

et al. 2020

Sci Rep

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the diagnosis of extrapulmonary tuberculosis (eptB) is often challenging due to paucibacillary nature of the disease. Xpert MtB/Rif Ultra (Ultra) has been developed to improve detection of Mycobacterium tuberculosis complex (Mtc) in paucibacillary specimens. the objective of the study was to assess the performance of Ultra for the diagnosis of eptB in a high-income low tB prevalence country. extrapulmonary samples received for tB diagnostics at two hospitals in norway between January 2015 and January 2016 were prospectively and consecutively included. Defrosted samples were subjected to Ultra. Culture and routine PCR tests were used as reference standard. A total of 82 samples, 10 culture and/or routine PCR positive (confirmed TB) samples and 72 culture and routine PCR negative samples were included in analysis. The overall sensitivity and specificity of Ultra were 90% (9/10, 95% CI 56-100) and 99% (71/72, 95% CI 93-100), respectively. Ultra was positive in 6/7 smear negative confirmed TB samples. To conclude, Ultra showed a high sensitivity and specificity in extrapulmonary specimens and may contribute to a rapid diagnosis of eptB in a low tB prevalence setting.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Xpert MTB/RIF ultra for rapid diagnosis of extrapulmonary tuberculosis in a high-income low-tuberculosis prevalence setting

Hoel

Syre

Skarstein

et al. 2020

Sci Rep

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“…TB/RIF Ultra is an advancement in the technique of Xpert with the addition of two different amplification targets. In a study by Donovan et al, the sensitivities of Xpert MTB/ RIF Ultra and Xpert MTB/RIF was 38.9 and 22.9 % in HIV negative tuberculous meningitis [32]. In a study by Yan et al, the sensitivity of metagenomic next-generation sequencing in the diagnosis of TBM was 84%, compared to 24.4 and 40 % with Mycobacterium PCR and Xpert MTB/RIF [33].…”

Section: Continuedmentioning

confidence: 99%

Comparative evaluation of IS6110 and protein antigen b PCR in cerebrospinal fluid for rapid diagnosis of tuberculous meningitis in children

Agarwal

Saini

Dhawan

et al. 2020

Journal of Medical Microbiology

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Introduction. Childhood tuberculosis meningitis is a severe form of tuberculosis with high morbidity and mortality. The diagnosis is frequently missed and delayed due to lack of sensitive tests like acid-fast bacilli (AFB) smear and delayed results by culture.Aims. To compare the role of IS6110 and protein antigen b PCR in cerebrospinal fluid (CSF) for rapid diagnosis of tuberculous meningitis (TBM) in children.Methodology. Forty-five cases of TBM and 20 controls were enrolled in this prospective study.Results. The mean ages of cases and controls were 4.2±0.5 years and 4.5±0.7 years, respectively. In the TBM group, two-thirds of the children were <4 years of age, and 62 % were males. Sensitivities of AFB smear examination, Löwenstein-Jensen (LJ) medium and bactenecin (BACTEC) culture in cases were 4.4, 0 and 2.2%, respectively. The protein antigen b PCR was most sensitive as it was positive in 35 (77.8 %) of TBM patients; IS6110 PCR was positive in 27 (60 %) patients. Both PCR-based tests had higher positivity than conventional tests and BACTEC culture. No significant difference was seen between the PCR tests. Excellent agreement was observed between both PCR-based tests as they were concordant for 26 positive samples and 35 negative samples.Conclusion. Protein b PCR is a sensitive and rapid method for the diagnosis of TBM (sensitivity 77.8 %). Both PCRs were more sensitive than smear, LJ and BACTEC. The specificity of both PCR was 100 %.

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“…GeneXpert Ultra has 70% sensitivity versus clinical case definition and misses up to 30% of cases [5]. However, a recent study from Donovan et al reported that GeneXpert Ultra was not superior to GeneXpert for TBM diagnosis in both HIV-uninfected and HIV-infected adults [6]. This attracted our interest to validate the diagnostic performance of GeneXpert for the diagnosis of TBM by using Mycobacterial Growth Indicator Tube (MGIT 960) as a gold standard.…”

Section: Introductionmentioning

confidence: 99%

Molecular diagnosis, genetic diversity and drug sensitivity patterns of Mycobacterium tuberculosis strains isolated from tuberculous meningitis patients at a tertiary care hospital in South India

Krishnakumariamma

Kalaiarasan

Muthuraj³

et al. 2020

PLoS ONE

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Tuberculous meningitis (TBM) is the most severe form of Mycobacterium tuberculosis (Mtb) infection in humans and is a public health concern worldwide. We evaluated the performance of GeneXpert MTB/RIF (GeneXpert) for the diagnosis of TBM. In addition, genetic diversity and drug susceptibility profiling of Mtb strains isolated from TBM patients were also investigated. A total of 293 TBM suspected cerebrospinal fluid (CSF) samples were collected and subjected to GeneXpert and Mycobacterial Growth Indicator Tube (MGIT 960) culture, respectively. Sensitivity and specificity of GeneXpert was 72.7% and 98.5%, respectively by using MGIT 960 as a gold standard (GeneXpert (n = 20, 6.8%) vs MGIT 960 (n = 22, 7.5%)). All Mtb positive cultures were subjected to 24-locus Mycobacterial Interspersed Repetitive Unit Variable Number Tandem Repeat (MIRU-VNTR) typing, Line probe assay (LPA) and MGIT 960-Drug Susceptibility Testing (DST). The rpoB gene was amplified and sequenced for selected isolates. Among our TBM patients, East African Indian (EAI) lineage (n = 16, 72.7%) was most predominant followed by Beijing (n = 3, 13.6%), Sfamily (n = 2, 9.1%) and Delhi/CAS (n = 1, 4.5%). Three Mtb strains were found to be Isoniazid (INH) resistant by MGIT 960; however LPA revealed that two strains were INH resistant and one strain was multi drug resistant (MDR) (Resistant to Isoniazid and Rifampicin (RIF)). We identified rifampicin resistant isolate with the mutation D516F in rifampicin resistancedetermining region (RRDR) and observed discordant results between LPA, GeneXpert and MGIT 960. In addition, GeneXpert showing false RIF resistance was identified (no mutation in RRDR). We conclude that GeneXpert is useful for the diagnostic confirmation of TBM; however a GeneXpert negative sample should be subjected to MGIT 960 culture or LPA to rule out TBM. EAI lineage was the most predominant among TBM patients in South India and associated with drug resistance. The discordance between GeneXpert, MGIT 960 and

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Xpert MTB/RIF Ultra versus Xpert MTB/RIF for the diagnosis of tuberculous meningitis: a prospective, randomised, diagnostic accuracy study

Cited by 101 publications

References 21 publications

Xpert MTB/RIF ultra for rapid diagnosis of extrapulmonary tuberculosis in a high-income low-tuberculosis prevalence setting

Xpert MTB/RIF ultra for rapid diagnosis of extrapulmonary tuberculosis in a high-income low-tuberculosis prevalence setting

Comparative evaluation of IS6110 and protein antigen b PCR in cerebrospinal fluid for rapid diagnosis of tuberculous meningitis in children

Molecular diagnosis, genetic diversity and drug sensitivity patterns of Mycobacterium tuberculosis strains isolated from tuberculous meningitis patients at a tertiary care hospital in South India

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