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Article ; Online: Applying a Standardized Approach to Strengthen Performances of GeneXpert Networks programme

Riccardo Alagna / T. Léon Sawadogo / Elisa Tagliani / Adjima Combary / Daniela Maria Cirillo

ERJ Open Research, Vol 6, Iss

lessons learned from Burkina Faso, 2019

2020 Volume 4

Abstract: GeneXpert scale-up is a historic step in the process of tuberculosis (TB) elimination. However, the global roll-out of the test has highlighted gaps that have limited its impact on the TB care cascade. Here we report the description of an innovative ... ...

Abstract	GeneXpert scale-up is a historic step in the process of tuberculosis (TB) elimination. However, the global roll-out of the test has highlighted gaps that have limited its impact on the TB care cascade. Here we report the description of an innovative GeneXpert network strengthening tool called Applying a Standardized Approach to Strengthen Performances of GeneXpert Networks (ASAP-GxNet) and highlight results and challenges during implementation of the pilot in Burkina Faso. ASAP-GxNet is a 6-month competency-based programme involving an innovative GeneXpert assessment tool as well as a series of short courses and projects designed to qualitatively improve the network while strengthening the capacity of the national GeneXpert focal point to oversee the network. Progress of the GeneXpert network is measured before and at the end of the programme and is rated using a star system (0 to 4 stars). In Burkina Faso, implementation of the ASAP-GxNet programme resulted in improved management of the national GeneXpert network with a 21% increase in points from the start to the end of the programme. To our knowledge, ASAP-GxNet is the first programme to give an overall picture of the quality of GeneXpert networks and to investigate performance in terms of management behaviour. ASAP-GxNet has been developed to help national TB programmes coordinate efforts and needs and highlights the expected achievements of the GeneXpert network.
Keywords	Medicine ; R
Subject code	000
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	European Respiratory Society
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Implementation of targeted next-generation sequencing for the diagnosis of drug-resistant tuberculosis in low-resource settings

Leonardo de Araujo / Andrea Maurizio Cabibbe / Lusia Mhuulu / Nunurai Ruswa / Viola Dreyer / Azaria Diergaardt / Gunar Günther / Mareli Claassens / Christiane Gerlach / Christian Utpatel / Daniela Maria Cirillo / Emmanuel Nepolo / Stefan Niemann

Frontiers in Public Health, Vol

a programmatic model, challenges, and initial outcomes

2023 Volume 11

Abstract: Targeted next-generation sequencing (tNGS) from clinical specimens has the potential to become a comprehensive tool for routine drug-resistance (DR) prediction of Mycobacterium tuberculosis complex strains (MTBC), the causative agent of tuberculosis (TB). ...

Abstract	Targeted next-generation sequencing (tNGS) from clinical specimens has the potential to become a comprehensive tool for routine drug-resistance (DR) prediction of Mycobacterium tuberculosis complex strains (MTBC), the causative agent of tuberculosis (TB). However, TB mainly affects low- and middle-income countries, in which the implementation of new technologies have specific needs and challenges. We propose a model for programmatic implementation of tNGS in settings with no or low previous sequencing capacity/experience. We highlight the major challenges and considerations for a successful implementation. This model has been applied to build NGS capacity in Namibia, an upper middle-income country located in Southern Africa and suffering from a high-burden of TB and TB-HIV, and we describe herein the outcomes of this process.
Keywords	Next generation sequencing (NGS) ; Mycobacterium tuberculosis complex (MTBC) ; NGS clinical use ; Genomic diagnostic ; Genomic surveillance ; NGS programmatic implementation ; Public aspects of medicine ; RA1-1270
Language	English
Publishing date	2023-08-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: ASAP-GxNet project in Burkina Faso

Riccardo Alagna / Tinnoga Lèon Sawadogo / Adjima Combary / Souba Diandé / Daniela Maria Cirillo

ERJ Open Research, Vol 5, Iss

fulfil country capacity gaps to ensure efficient utilisation of GeneXpert instruments in tuberculosis care and cascade

2019 Volume 1

Keywords	Medicine ; R
Language	English
Publishing date	2019-02-01T00:00:00Z
Publisher	European Respiratory Society
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Updating the WHO target product profile for next-generation Mycobacterium tuberculosis drug susceptibility testing at peripheral centres.

Emily Lai-Ho MacLean / Paolo Miotto / Lice González Angulo / Matteo Chiacchiaretta / Timothy M Walker / Martina Casenghi / Camilla Rodrigues / Timothy C Rodwell / Philip Supply / Emmanuel André / Mikashmi Kohli / Morten Ruhwald / Daniela Maria Cirillo / Nazir Ismail / Matteo Zignol

PLOS Global Public Health, Vol 3, Iss 3, p e

2023 Volume 0001754

Abstract: There were approximately 10 million tuberculosis (TB) cases in 2020, of which 500,000 were drug-resistant. Only one third of drug-resistant TB cases were diagnosed and enrolled on appropriate treatment, an issue partly driven by a lack of rapid, accurate ...

Abstract	There were approximately 10 million tuberculosis (TB) cases in 2020, of which 500,000 were drug-resistant. Only one third of drug-resistant TB cases were diagnosed and enrolled on appropriate treatment, an issue partly driven by a lack of rapid, accurate drug-susceptibility testing (DST) tools deployable in peripheral settings. In 2014, World Health Organization (WHO) published target product profiles (TPPs) which detailed minimal and optimal criteria to address high-priority TB diagnostic needs, including DST. Since then, the TB community's needs have evolved; new treatment regimens, changes in TB definitions, further emergence of drug resistance, technological advances, and changing end-users requirements have necessitated an update. The DST TPP's revision was therefore undertaken by WHO with the Stop TB Partnership New Diagnostics Working Group. We describe the process of updating the TPP for next-generation TB DST for use at peripheral centres, highlight key updates, and discuss guidance regarding technical and operational specifications.
Keywords	Public aspects of medicine ; RA1-1270
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Whole genome sequencing of multidrug-resistant Mycobacterium tuberculosis isolates collected in the Czech Republic, 2005–2020

Matúš Dohál / Věra Dvořáková / Miluše Šperková / Martina Pinková / Andrea Spitaleri / Anders Norman / Andrea Maurizio Cabibbe / Erik Michael Rasmussen / Igor Porvazník / Mária Škereňová / Ivan Solovič / Daniela Maria Cirillo / Juraj Mokrý

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 10

Abstract: Abstract The emergence and spread of resistant tuberculosis (TB) pose a threat to public health, so it is necessary to diagnose the drug-resistant forms in a clinically short time frame and closely monitor their transmission. In this study, we carried ... ...

Abstract	Abstract The emergence and spread of resistant tuberculosis (TB) pose a threat to public health, so it is necessary to diagnose the drug-resistant forms in a clinically short time frame and closely monitor their transmission. In this study, we carried out a first whole genome sequencing (WGS)-based analysis of multidrug resistant (MDR) M. tuberculosis strains to explore the phylogenetic lineages diversity, drug resistance mechanisms, and ongoing transmission chains within the country. In total, 65 isolates phenotypically resistant to at least rifampicin and isoniazid collected in the Czech Republic in 2005–2020 were enrolled for further analysis. The agreement of the results obtained by WGS with phenotypic drug susceptibility testing (pDST) in the determination of resistance to isoniazid, rifampicin, pyrazinamide, streptomycin, second-line injectables and fluoroquinolones was more than 80%. Phylogenetic analysis of WGS data revealed that the majority of MDR M. tuberculosis isolates were the Beijing lineage 2.2.1 (n = 46/65; 70.8%), while the remaining strains belonged to Euro-American lineage. Cluster analysis with a predefined cut-off distance of less than 12 single nucleotide polymorphisms between isolates showed 19 isolates in 6 clusters (clustering rate 29.2%), located mainly in the region of the capital city of Prague. This study highlights the utility of WGS as a high-resolution approach in the diagnosis, characterization of resistance patterns, and molecular-epidemiological analysis of resistant TB in the country.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Fragmentation of Healthcare Services as a Possible Determinant of the Low Completion for the Tuberculosis Cascade of Prevention among Asylum Seekers

Valentina Marchese / Paola Zanotti / Claudia Cimaglia / Benedetta Rossi / Beatrice Formenti / Paola Magro / Maurizio Gulletta / Giovanna Stancanelli / Issa El-Hamad / Enrico Girardi / Daniela Maria Cirillo / Francesco Castelli / Alberto Matteelli

Pathogens, Vol 11, Iss 613, p

Results from a Prospective Study with Historical Comparison

2022 Volume 613

Abstract: Background: Effective screening for tuberculosis infection (TBI) among asylum seekers (AS) is crucial for tuberculosis (TB) elimination in low incidence countries. Methods: We assessed the proportion of completion of the screening for TBI among asylum ... ...

Abstract	Background: Effective screening for tuberculosis infection (TBI) among asylum seekers (AS) is crucial for tuberculosis (TB) elimination in low incidence countries. Methods: We assessed the proportion of completion of the screening for TBI among asylum seekers with a centralized delivery method compared to the decentralized model previously adopted in the study area (historical control). In the historical model (January 2017 to May 2018) screening of AS was performed at the arrival offering TBI testing (TST followed by IGRA among those positive), radiological investigation, treatment initiation and hospital referral, if needed, at three sites: migrant health clinic, pneumology clinic and infectious diseases department for active disease (decentralized model). In the study model (June 2018, centralized) all steps of screening were performed at a single site, at a minimum of 6 months after arrival. Multivariable Poisson regression analysis, with robust variance, was used to assess variables associated with the completion of screening for infection. Multivariable logistic regression was used to identify factors associated with the diagnosis of TB infection. Results: The intervention approach was offered to 144 AS with an overall 98.6% proportion of completion (98.7% for those with a positive TST). In the historical screening model, 1192 AS were candidates for screening, which was completed by 74.5% of those who started it (44.7% for those resulted TST positive). Major losses (55%) were detected in the TST/CXR-IGRA sequential step, followed by the execution of TST test (25%). The ratio of screening completion was significantly higher in the intervention period (aIRR 1.78, 95% CI 1.68–1.88) and for AS coming from high incidence TB countries (aIRR 1.14, 95% CI 1.04–1.25). Screening after 6 months from arrival and age were associated with TB infection (2.09, 95% CI 1.36–3.2 and 1.14, 95% CI 1.01–1.29). Conclusions: Screening for TBI can be improved by a centralized approach. Higher prevalence of TBI 6 months after ...
Keywords	tuberculosis ; migrant ; Europe ; TB infection ; LTBI ; healthcare delivery ; Medicine ; R
Subject code	630
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Bedaquiline Phenotypic and Genotypic Susceptibility Testing, Work in Progress!

Simon Tiberi / Andrea Maurizio Cabibbe / Jennifer Tomlins / Daniela Maria Cirillo / Giovanni Battista Migliori

EBioMedicine, Vol 29, Iss , Pp 11-

2018 Volume 12

Keywords	Medicine ; R ; Medicine (General) ; R5-920
Language	English
Publishing date	2018-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: MTBseq

Thomas Andreas Kohl / Christian Utpatel / Viola Schleusener / Maria Rosaria De Filippo / Patrick Beckert / Daniela Maria Cirillo / Stefan Niemann

PeerJ, Vol 6, p e

a comprehensive pipeline for whole genome sequence analysis of Mycobacterium tuberculosis complex isolates

2018 Volume 5895

Abstract: Analyzing whole-genome sequencing data of Mycobacterium tuberculosis complex (MTBC) isolates in a standardized workflow enables both comprehensive antibiotic resistance profiling and outbreak surveillance with highest resolution up to the identification ... ...

Abstract	Analyzing whole-genome sequencing data of Mycobacterium tuberculosis complex (MTBC) isolates in a standardized workflow enables both comprehensive antibiotic resistance profiling and outbreak surveillance with highest resolution up to the identification of recent transmission chains. Here, we present MTBseq, a bioinformatics pipeline for next-generation genome sequence data analysis of MTBC isolates. Employing a reference mapping based workflow, MTBseq reports detected variant positions annotated with known association to antibiotic resistance and performs a lineage classification based on phylogenetic single nucleotide polymorphisms (SNPs). When comparing multiple datasets, MTBseq provides a joint list of variants and a FASTA alignment of SNP positions for use in phylogenomic analysis, and identifies groups of related isolates. The pipeline is customizable, expandable and can be used on a desktop computer or laptop without any internet connection, ensuring mobile usage and data security. MTBseq and accompanying documentation is available from https://github.com/ngs-fzb/MTBseq_source.
Keywords	Next-generation sequencing ; Mycobacterium tuberculosis complex ; Phylogeny ; Whole-genome sequencing ; Automated analysis pipeline ; Bacterial genome analysis ; Medicine ; R ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2018-11-01T00:00:00Z
Publisher	PeerJ Inc.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Whole Genome Sequencing Results Associated with Minimum Inhibitory Concentrations of 14 Anti-Tuberculosis Drugs among Rifampicin-Resistant Isolates of Mycobacterium Tuberculosis from Iran

Jalil Kardan-Yamchi / Hossein Kazemian / Simone Battaglia / Hamidreza Abtahi / Abbas Rahimi Foroushani / Gholamreza Hamzelou / Daniela Maria Cirillo / Arash Ghodousi / Mohammad Mehdi Feizabadi

Journal of Clinical Medicine, Vol 9, Iss 2, p

2020 Volume 465

Abstract: Accurate and timely detection of drug resistance can minimize the risk of further resistance development and lead to effective treatment. The aim of this study was to determine the resistance to first/second-line anti-tuberculosis drugs in rifampicin/ ... ...

Abstract	Accurate and timely detection of drug resistance can minimize the risk of further resistance development and lead to effective treatment. The aim of this study was to determine the resistance to first/second-line anti-tuberculosis drugs in rifampicin/multidrug-resistant Mycobacterium tuberculosis (RR/MDR-MTB) isolates. Molecular epidemiology of strains was determined using whole genome sequencing (WGS)-based genotyping. A total of 35 RR/MDR-MTB isolates were subjected to drug susceptibility testing against first/second-line drugs using 7H9 Middlebrook in broth microdilution method. Illumina technology was used for paired-end WGS applying a Maxwell 16 Cell DNA Purification kit and the NextSeq platform. Data analysis and single nucleotide polymorphism calling were performed using MTBseq pipeline. The genome-based resistance to each drug among the resistant phenotypes was as follows: rifampicin (97.1%), isoniazid (96.6%), ethambutol (100%), levofloxacin (83.3%), moxifloxacin (83.3%), amikacin (100%), kanamycin (100%), capreomycin (100%), prothionamide (100%), D-cycloserine (11.1%), clofazimine (20%), bedaquiline (0.0%), and delamanid (44.4%). There was no linezolid-resistant phenotype, and a bedaquiline-resistant strain was wild type for related genes. The Beijing, Euro-American, and Delhi-CAS were the most populated lineage/sublineages. Drug resistance-associated mutations were mostly linked to minimum inhibitory concentration results. However, the role of well-known drug-resistant genes for D-cycloserine, clofazimine, bedaquiline, and delamanid was found to be more controversial.
Keywords	mycobacterium tuberculosis ; drug resistance ; mutation ; gene ; minimum inhibitory concentration ; whole genome sequencing ; Medicine ; R
Language	English
Publishing date	2020-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Genomic analysis of cardiac surgery-associated Mycobacterium chimaera infections in Italy.

Arash Ghodousi / Emanuele Borroni / Marta Peracchi / Giorgio Palù / Loredana Fallico / Mario Rassu / Vinicio Manfrin / Paola Mantegani / Vincenzina Monzillo / Riccardo Manganelli / Enrico Tortoli / Daniela Maria Cirillo

PLoS ONE, Vol 15, Iss 9, p e

2020 Volume 0239273

Abstract: One hundred and twenty-two Mycobacterium chimaera strains isolated in Italy from cardiac surgery-related patients, cardiac surgery-unrelated patients and from heater-cooler units, were submitted to whole-genome sequencing and to subsequent SNP analysis. ... ...

Abstract	One hundred and twenty-two Mycobacterium chimaera strains isolated in Italy from cardiac surgery-related patients, cardiac surgery-unrelated patients and from heater-cooler units, were submitted to whole-genome sequencing and to subsequent SNP analysis. All but one strains isolated from cardiac surgery-related patients belonged to Subgroup 1.1 (19/23) or Subgroup 1.8 (3/23). Only 28 out of 79 strains isolated from heater-cooler units belonged to groupings other than 1.1 and 1.8. The strains isolated from cardiac surgery-unrelated patients were instead distributed across the phylogenetic tree. Our data, the first on isolates from Italy, are in agreement with a recent large genomic study suggesting a common source, represented by strains belonging to Subgroups 1.1 and 1.8, of cardiac surgery-related Mycobacterium chimaera infections. The strains belonging to groupings other than 1.1 and 1.8 isolated from heather-cooler units evidently resulted from contaminations at hospital level and had no share in the Mycobacterium chimaera outbreak. One Mycobacterium chimaera strain investigated in this study proved distant from every previously known Mycobacterium chimaera Groups (1, 2, 3 and 4) and we propose to assign to a novel group, named "Group 5".
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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