Pooling sputum for Xpert MTB/RIF and Xpert Ultra testing during the Covid-19 pandemic in Lao People’s Democratic Republic

Iem, Vibol; Chittamany, Phonenaly; Suthepmany, Sakhone; Siphanthong, Souvimone; Somphavong, Silaphet; Kontogianni, Konstantina; Dodd, James; Khan, Jahangir Akber Mahmud; Domínguez, José; Wingfield, Tom; Creswell, Jacob; Cuevas, Luís E.

doi:10.1371/journal.pgph.0000116

Cited by 7 publications

(8 citation statements)

References 22 publications

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“…In 2015, due to drug resistance rising worldwide, the WHO proposed expanding rapid testing and detection of cases as one of the five high-priority actions to tackle the global DR-TB crisis [15]. As part of these actions, some molecular biology-based diagnostic methods have been applied in a clinical setting for their versatility and speed, including variants of Xpert MTB/RIF and Geno-Type MTBDRplus [16][17][18][19]. Although these methods are rapid and straightforward, Mtb continuously evolves through the genomic acquisition of single nucleotide polymorphisms (SNPs), insertions, and deletions (indels), impacting the ability to discriminate strains without the classic regions used for resistance detection [20].…”

Section: Introductionmentioning

confidence: 99%

Comparative genomics of drug-resistant strains of Mycobacterium tuberculosis in Ecuador

et al. 2022

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Background Tuberculosis is a serious infectious disease affecting millions of people. In spite of efforts to reduce the disease, increasing antibiotic resistance has contributed to persist in the top 10 causes of death worldwide. In fact, the increased cases of multi (MDR) and extreme drug resistance (XDR) worldwide remains the main challenge for tuberculosis control. Whole genome sequencing is a powerful tool for predicting drug resistance-related variants, studying lineages, tracking transmission, and defining outbreaks. This study presents the identification and characterization of resistant clinical isolates of Mycobacterium tuberculosis including a phylogenetic and molecular resistance profile study by sequencing the complete genome of 24 strains from different provinces of Ecuador. Results Genomic sequencing was used to identify the variants causing resistance. A total of 15/21 isolates were identified as MDR, 4/21 as pre-XDR and 2/21 as XDR, with three isolates discarded due to low quality; the main sub-lineage was LAM (61.9%) and Haarlem (19%) but clades X, T and S were identified. Of the six pre-XDR and XDR strains, it is noteworthy that five come from females; four come from the LAM sub-lineage and two correspond to the X-class sub-lineage. A core genome of 3,750 genes, distributed in 295 subsystems, was determined. Among these, 64 proteins related to virulence and implicated in the pathogenicity of M. tuberculosis and 66 possible pharmacological targets stand out. Most variants result in nonsynonymous amino acid changes and the most frequent genotypes were identified as conferring resistance to rifampicin, isoniazid, ethambutol, para-aminosalicylic acid and streptomycin. However, an increase in the resistance to fluoroquinolones was detected. Conclusion This work shows for the first time the variability of circulating resistant strains between men and women in Ecuador, highlighting the usefulness of genomic sequencing for the identification of emerging resistance. In this regard, we found an increase in fluoroquinolone resistance. Further sampling effort is needed to determine the total variability and associations with the metadata obtained to generate better health policies.

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Section: Introductionmentioning

confidence: 99%

Comparative genomics of drug-resistant strains of Mycobacterium tuberculosis in Ecuador

et al. 2022

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“…In this cost-effectiveness analysis, a total of 3,076 individuals with presumptive TB were enrolled from two studies conducted in Lao PDR (840 individuals per study) [ 8 ], two studies in Nigeria (500 individuals per study) (Bimba et al in press), and one study in Brazil (396 individuals) [ 9 ], which are described in more detail below.…”

Section: Methodsmentioning

confidence: 99%

“…In Lao PDR [ 8 ] and Nigeria (Bimba et al in press), two independent studies were conducted during PCF of people with presumptive TB, one using Xpert MTB/RIF, and the other Ultra. The study from Brazil assessed the performance of pooled testing with Xpert Ultra only [ 9 ].…”

Section: Methodsmentioning

confidence: 99%

Pooling sputum testing to diagnose tuberculosis using xpert MTB/RIF and xpert ultra: a cost-effectiveness analysis

et al. 2023

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Background The World Health Organization (WHO) recommends the diagnosis of tuberculosis (TB) using molecular tests, such as Xpert MTB/RIF (MTB/RIF) or Xpert Ultra (Ultra). These tests are expensive and resource-consuming, and cost-effective approaches are needed for greater coverage. Methods We evaluated the cost-effectiveness of pooling sputum samples for TB testing by using a fixed amount of 1,000 MTB/RIF or Ultra cartridges. We used the number of people with TB detected as the indicator for cost-effectiveness. Cost-minimization analysis was conducted from the healthcare system perspective and included the costs to the healthcare system using pooled and individual testing. Results There was no significant difference in the overall performance of the pooled testing using MTB/RIF or Ultra (sensitivity, 93.9% vs. 97.6%, specificity 98% vs. 97%, p-value > 0.1 for both). The mean unit cost across all studies to test one person was 34.10 international dollars for the individual testing and 21.95 international dollars for the pooled testing, resulting in a savings of 12.15 international dollars per test performed (35.6% decrease). The mean unit cost per bacteriologically confirmed TB case was 249.64 international dollars for the individual testing and 162.44 international dollars for the pooled testing (34.9% decrease). Cost-minimization analysis indicates savings are directly associated with the proportion of samples that are positive. If the TB prevalence is ≥ 30%, pooled testing is not cost-effective. Conclusion Pooled sputum testing can be a cost-effective strategy for diagnosis of TB, resulting in significant resource savings. This approach could increase testing capacity and affordability in resource-limited settings and support increased testing towards achievement of WHO End TB strategy.

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“…In a systematic review of studies where each specimen was tested both individually and in pools, Cuevas et al reported that the positive percent agreement for pools of four samples as compared with individual samples was 91% for the Xpert MTB/RIF assay and 98% for the Xpert MTB/RIF Ultra assay 39 . Subsequent studies have reported similarly small reductions in testing accuracy with large improvements in testing efficiency and significant cartridge and cost savings when using these assays for pooled testing for TB detection 36 , 37 , 40 . However, despite these results that highlight the good potential value of pooled testing to improve the detection of TB, pooled testing has not yet been widely adopted to increase molecular testing coverage for routine TB diagnosis.…”

Section: Introductionmentioning

confidence: 92%

Implementation of large-scale pooled testing to increase rapid molecular diagnostic test coverage for tuberculosis: a retrospective evaluation

Vuchas,

Teyim,

Dang

et al. 2023

Sci Rep

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In 2021, only 6.4 million of the 10.6 million people with tuberculosis (TB) were diagnosed and treated for the disease. Although the World Health Organization recommends initial diagnostic testing using a rapid sensitive molecular assay, only 38% of people diagnosed with TB benefited from these, due to barriers including the high cost of available assays. Pooled testing has been used as an approach to increase testing efficiency in many resource-constrained situations, such as the COVID-19 pandemic, but it has not yet been widely adopted for TB diagnostic testing. Here we report a retrospective analysis of routine pooled testing of 10,117 sputum specimens using the Xpert MTB/RIF and Xpert MTB/RIF Ultra assays that was performed from July 2020 to February 2022. Pooled testing saved 48% of assays and enabled rapid molecular testing for 4156 additional people as compared to individual testing, with 6.6% of specimens positive for TB. From an in silico analysis, the positive percent agreement of pooled testing in pools of 3 as compared with individual testing for the Xpert MTB/RIF Ultra assay was estimated as 99.4% (95% CI, 96.6% to 100%). These results support the scale-up of pooled testing for efficient TB diagnosis.

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Pooling sputum for Xpert MTB/RIF and Xpert Ultra testing during the Covid-19 pandemic in Lao People’s Democratic Republic

Cited by 7 publications

References 22 publications

Comparative genomics of drug-resistant strains of Mycobacterium tuberculosis in Ecuador

Comparative genomics of drug-resistant strains of Mycobacterium tuberculosis in Ecuador

Pooling sputum testing to diagnose tuberculosis using xpert MTB/RIF and xpert ultra: a cost-effectiveness analysis

Implementation of large-scale pooled testing to increase rapid molecular diagnostic test coverage for tuberculosis: a retrospective evaluation

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