Patients With Tuberculosis, Mycobacteriosis or Latent Tuberculosis

Epidemiological, Demographic and Clinical Aspects of Patients With Tuberculosis, Mycobacteriosis or Infection Latent Tuberculosis

In the last 30 years, tuberculosis (TB) has re-emerged in industrialised countries as a public health, with a decrease in incidence among the resident population and an increase in the burden of immigrants. Therefore, it becomes a priority to implement an effective TB control that relies on both rapid and reliable identification of active infections, with a adequate treatment and surveillance of resistance, but also on the identification of latent tuberculosis infections (ITBL) in populations at higher risk of progression to the active disease, representing a source of infection for the community.

Study Overview

• Status: Recruiting
• Conditions: Mycobacterial Infection; Tuberculosis (TB)

Detailed Description

The study is non-pharmacological and monocentric. Data from patients with clinical/radiological suspicion of mycobacteriosis or tuberculosis will be considered for which they have been received at the OU of Microbiology of the Polyclinic S.Orsola-Malpighi biological samples for mycobacteria research and/or blood samples for immunological investigations for latent tubercular infection in the period January 2012-May 2021 (retrospective part of the study); Data from patients suspected of mycobacteriosis, TB or ITBL from June 2021 to December 2026 (prospective part of the study, duration: 6 years, possibly renewable) will also be considered. The objectives of the study are: 1) Analysis of epidemiological, demographic and clinical aspects of patients with TB, mycobacteriosis non-tubercular or ITBL in the period January 2012-December 2026. 2) Assessment of diagnostic accuracy of the most frequently used methods for Microbiological diagnosis of tuberculosis (TB) or non-tubercular mycobacteriosis and immunological methods for the diagnosis of latent tubercular infection (ITBL). 3) Analysis of the microbiological characteristics (phenotypic and molecular) of MTB and NTM strains. 4) Evaluation of the clinical outcome of patients with ITBL/TB/NTM in treatment and follow-up in the post-treatment period.

• Study Type: Observational
• Enrollment (Estimated): 13000

Contacts and Locations

• Study Contact: Name: Paola Dal Monte, MD; Phone Number: 0390512145293; Email: paola.dalmonte@unibo.it

Study Locations

• Italy
  • Bologna, Italy, 40138
    • Recruiting
    • IRCCS Azienda Ospedaliero-Universitaria di Bologna
    • Contact: Paola Dal Monte, MD; Phone Number: +390512145293; Email: paola.dalmonte@unibo.it
    • Sub-Investigator: Giulia Lombardi
    • Sub-Investigator: Francesco Bisognin
    • Sub-Investigator: Marina Tadolini, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

For the retrospective phase: TB or mycobacteriosis cases confirmed and ITBL cases followed by Infectious Disease Unit.

For the prospective phase: TB, non-tubercular mycobacteriosis or ITBL patients with suspicion.

Description

Inclusion Criteria:

• age of 18 years or more,
• clinical/radiological suspicion of TB or non-tubercular mycobacteriosis or ITBL for which sent to the Microbiology laboratory at least one biological sample for the mycobacteria and/or a blood sample for the IGRA test;
• Obtaining informed consent.

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Tuberculosis or mycobacteriosis Microbiologically confirmed cases; Retrospective phase from 1 January 2012 to 31 May 2021
Latent tuberculosis infection cases; Retrospective phase, patients followed by infectious diseases clinics from 2017 to May 2021
Patients with suspected tuberculosis, non-tubercular mycobacteriosis or tubercular infection; Prospective phase from 1 June 2021 to 31 December 2026

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analysis of epidemiological, demographic and clinical aspects of patients with tuberculosis, mycobacteriosis non-tubercular or latent tubercular infection	Patients' data with biological samples for mycobacteria research and/or blood samples for immunological investigations for latent tubercular infection and clinical/radiological suspicion of mycobacteriosis or tuberculosis had been colleted from January 2012 to May 2021 (retrospective phase of the study) and from June 2021 to December 2026 (prospective phase of the study). The criteria for diagnosis of TB confirmed microbiologically are: Clinical+Imaging suggestive of tuberculosis disease;microbiological isolation of MTB and/ or molecular test for MTB (Xpert) positive;decision of the clinician to start anti-tuberculosis treatment. The criteria for diagnosing non-tubercular mycobacteriosis are: Clinical+Imaging suggestive of mycobacteriosis;isolation of NTM from at least two sputum samples or one bronchocolagement sample. The criteria for diagnosing ITBL are: positive IGRA and/or positive TST test;absence of clinical/radiological signs of tubercular disease.	from 2021 to 2026

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of the diagnostic accuracy of the most frequently used methods for microbiological diagnosis of tuberculosis (TB) or non-tubercular mycobacteriosis and Immunological methods for the diagnosis of latent tubercular infection (ITBL).	Patients' data with biological samples for mycobacteria research and/or blood samples for immunological investigations for latent tubercular infection and clinical/radiological suspicion of mycobacteriosis or tuberculosis had been colleted from January 2012 to May 2021 (retrospective phase of the study) and from June 2021 to December 2026 (prospective phase of the study). The criteria for diagnosis of TB confirmed microbiologically are: Clinical+Imaging suggestive of tuberculosis disease;microbiological isolation of MTB and/ or molecular test for MTB (Xpert) positive;decision of the clinician to start anti-tuberculosis treatment. The criteria for diagnosing non-tubercular mycobacteriosis are: Clinical+Imaging suggestive of mycobacteriosis;isolation of NTM from at least two sputum samples or one bronchocolagement sample. The criteria for diagnosing ITBL are: positive IGRA and/or positive TST test;absence of clinical/radiological signs of tubercular disease.	from 2021 to 2026

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analysis of the microbiological characteristics (phenotypic and molecular) of MTB and NTM.	Patients' data with biological samples for mycobacteria research and/or blood samples for immunological investigations for latent tubercular infection and clinical/radiological suspicion of mycobacteriosis or tuberculosis had been colleted from January 2012 to May 2021 (retrospective phase of the study) and from June 2021 to December 2026 (prospective phase of the study). The criteria for diagnosis of TB confirmed microbiologically are: Clinical+Imaging suggestive of tuberculosis disease;microbiological isolation of MTB and/ or molecular test for MTB (Xpert) positive;decision of the clinician to start anti-tuberculosis treatment. The criteria for diagnosing non-tubercular mycobacteriosis are: Clinical+Imaging suggestive of mycobacteriosis;isolation of NTM from at least two sputum samples or one bronchocolagement sample. The criteria for diagnosing ITBL are: positive IGRA and/or positive TST test;absence of clinical/radiological signs of tubercular disease.	from 2021 to 2026
Evaluation of the clinical outcome of patients with ITBL/TB/NTM in treatment and follow-up in post-processing period.	Patients' data with biological samples for mycobacteria research and/or blood samples for immunological investigations for latent tubercular infection and clinical/radiological suspicion of mycobacteriosis or tuberculosis had been colleted from January 2012 to May 2021 (retrospective phase of the study) and from June 2021 to December 2026 (prospective phase of the study). The criteria for diagnosis of TB confirmed microbiologically are: Clinical+Imaging suggestive of tuberculosis disease;microbiological isolation of MTB and/ or molecular test for MTB (Xpert) positive;decision of the clinician to start anti-tuberculosis treatment. The criteria for diagnosing non-tubercular mycobacteriosis are: Clinical+Imaging suggestive of mycobacteriosis;isolation of NTM from at least two sputum samples or one bronchocolagement sample. The criteria for diagnosing ITBL are: positive IGRA and/or positive TST test;absence of clinical/radiological signs of tubercular disease.	from 2021 to 2026

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Investigators: Principal Investigator: Paola Dal Monte, MD, IRCCS Azienda Ospedaliero-Universitaria di Bologna

Publications and helpful links

General Publications

• Haworth CS, Banks J, Capstick T, Fisher AJ, Gorsuch T, Laurenson IF, Leitch A, Loebinger MR, Milburn HJ, Nightingale M, Ormerod P, Shingadia D, Smith D, Whitehead N, Wilson R, Floto RA. British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD). Thorax. 2017 Nov;72(Suppl 2):ii1-ii64. doi: 10.1136/thoraxjnl-2017-210927. No abstract available.
• Nahid P, Dorman SE, Alipanah N, Barry PM, Brozek JL, Cattamanchi A, Chaisson LH, Chaisson RE, Daley CL, Grzemska M, Higashi JM, Ho CS, Hopewell PC, Keshavjee SA, Lienhardt C, Menzies R, Merrifield C, Narita M, O'Brien R, Peloquin CA, Raftery A, Saukkonen J, Schaaf HS, Sotgiu G, Starke JR, Migliori GB, Vernon A. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis. Clin Infect Dis. 2016 Oct 1;63(7):e147-e195. doi: 10.1093/cid/ciw376. Epub 2016 Aug 10.
• Petrucci R, Lombardi G, Corsini I, Bacchi Reggiani ML, Visciotti F, Bernardi F, Landini MP, Cazzato S, Dal Monte P. Quantiferon-TB Gold In-Tube Improves Tuberculosis Diagnosis in Children. Pediatr Infect Dis J. 2017 Jan;36(1):44-49. doi: 10.1097/INF.0000000000001350.
• Barcellini L, Borroni E, Brown J, Brunetti E, Codecasa L, Cugnata F, Dal Monte P, Di Serio C, Goletti D, Lombardi G, Lipman M, Rancoita PM, Tadolini M, Cirillo DM. First independent evaluation of QuantiFERON-TB Plus performance. Eur Respir J. 2016 May;47(5):1587-90. doi: 10.1183/13993003.02033-2015. Epub 2016 Feb 11. No abstract available.
• Dorman SE, Schumacher SG, Alland D, Nabeta P, Armstrong DT, King B, Hall SL, Chakravorty S, Cirillo DM, Tukvadze N, Bablishvili N, Stevens W, Scott L, Rodrigues C, Kazi MI, Joloba M, Nakiyingi L, Nicol MP, Ghebrekristos Y, Anyango I, Murithi W, Dietze R, Lyrio Peres R, Skrahina A, Auchynka V, Chopra KK, Hanif M, Liu X, Yuan X, Boehme CC, Ellner JJ, Denkinger CM; study team. Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study. Lancet Infect Dis. 2018 Jan;18(1):76-84. doi: 10.1016/S1473-3099(17)30691-6. Epub 2017 Nov 30. Erratum In: Lancet Infect Dis. 2018 Apr;18(4):376. doi: 10.1016/S1473-3099(18)30169-5.
• Lombardi G, Di Gregori V, Girometti N, Tadolini M, Bisognin F, Dal Monte P. Diagnosis of smear-negative tuberculosis is greatly improved by Xpert MTB/RIF. PLoS One. 2017 Apr 21;12(4):e0176186. doi: 10.1371/journal.pone.0176186. eCollection 2017.
• Internal Clinical Guidelines Team (UK). Tuberculosis: Prevention, Diagnosis, Management and Service Organisation. London: National Institute for Health and Care Excellence (UK); 2016 Jan. Available from http://www.ncbi.nlm.nih.gov/books/NBK338750/
• Jensen PA, Lambert LA, Iademarco MF, Ridzon R; CDC. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005. MMWR Recomm Rep. 2005 Dec 30;54(RR-17):1-141.
• Aliberti S, Codecasa LR, Gori A, Sotgiu G, Spotti M, Di Biagio A, Calcagno A, Nardini S, Assael BM, Tortoli E, Besozzi G, Ferrarese M, Matteelli A, Girardi E, De Lorenzo S, Seia M, Gramegna A, Del Prato B, Terranova L, Oriano M, Sverzellati N, Mirsaeidi M, Chalmers JD, Haworth CS, Loebinger MR, Aksamit T, Winthrop K, Ringshausen FC, Previdi G, Blasi F; IRENE Network. The Italian registry of pulmonary non-tuberculous mycobacteria - IRENE: the study protocol. Multidiscip Respir Med. 2018 Aug 9;13(Suppl 1):33. doi: 10.1186/s40248-018-0141-8. eCollection 2018.
• Fattorini L, Mustazzolu A, Borroni E, Piccaro G, Giannoni F, Cirillo DM; Italian Multicentre Study on Resistance to Antituberculosis Drugs (SMIRA) Group. Tuberculosis in migrants from 106 countries to Italy, 2008-2014. Eur Respir J. 2016 Apr;47(4):1273-6. doi: 10.1183/13993003.01844-2015. Epub 2016 Feb 4. No abstract available.
• Lombardi G, Dal Monte P, Denicolo A, Tadolini M, Martelli G, Bacchi Reggiani ML, Viale P, Landini MP. Trend of microbiologically-confirmed tuberculosis in a low-incidence setting with high immigration rates. BMC Public Health. 2014 Apr 10;14:340. doi: 10.1186/1471-2458-14-340.

Helpful Links

• Agenzia Sanitaria e Sociale Regionale della Regione Emilia-Romagna. Epidemiologia della tubercolosi in Emilia-Romagna 2010-11.
• World Health Organization. Guidelines for the treatment of drug-susceptible tuberculosis and patient care (2017 update)
• Clinical and Laboratory Standards Institute. M48-A Laboratory detection and identification of mycobacteria

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: January 2, 2025
• First Submitted That Met QC Criteria: January 2, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 2, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: infection; diagnosis; tuberculosis; latent tuberculosis infection; microbiological tests; mycobacterial; mycobacterial non-tubercular
• Additional Relevant MeSH Terms: Latent Infection; Pathologic Processes; Disease Attributes; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Infections; Communicable Diseases; Mycobacterium Infections; Tuberculosis; Latent Tuberculosis
• Other Study ID Numbers: Micro-TB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No