Demonstration of the Dynamic Hypothesis of Latent Tuberculosis Infection (HYPDYN)

It is traditionally considered that the development of Latent Tuberculosis Infection (LTBI) is due to the M. tuberculosis ability to develop a dormancy state within well-structured lesions (granulomas), which can remain in the lung of the host even for life. A new original hypothesis has been developed in the Experimental Tuberculosis Unit based on scientific evidence that take into account the idea that a lesion cannot be held forever, because the host tends to remove any lesion in order to rebuild the original parenchyma, in a healing process. Even if M. tuberculosis can remain in a dormant/non-replicating state for a long period, this is an important but not sufficient factor to explain the LTBI. The Dynamic Hypothesis tries to explain the existence of LTBI in spite of the healing process that could remove it by a constant reinfection of the host's tissue. While the "Static" view defends the induction of active TB after the reactivation of the bacilli from and old lesion; while the "Dynamic" view wants to demonstrate that there is a constant induction of new granulomas. In case one of these new lesions takes place in the upper lobe privileged zone, the possibility to induce a cavity would appear, developing an active Tuberculosis (TB).

Study Overview

• Status: Unknown
• Conditions: Latent Tuberculosis Infection

• Study Type: Observational
• Enrollment (Anticipated): 105

Contacts and Locations

• Study Contact: Name: Cristina Vilaplana, MD; Phone Number: +3493497861; Email: cvilaplana@gmail.com
• Study Contact Backup: Name: Pere-Joan Cardona, MD, PhD; Phone Number: +34934978686; Email: pjcardona.igtp.germanstrias@gencat.cat

Study Locations

• Spain
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Recruiting
      • Fundació Institut Germans Trias i Pujol
      • Sub-Investigator: Cristina Vilaplana, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Latent Tuberculosis Infected people

Description

Inclusion Criteria:

• being at least 18 years old
• to be M.tuberculosis infected (diagnosed by a positive TST with or without a positive result in the QuantiFeron-TB-Gold In tube assay)

Exclusion Criteria:

• active TB
• individuals not willing to participate in the study and or not willing to sign the informed consent form
• individuals not able to decide their participation in the study

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
1; Patients with LTBI recently diagnosed under prophylactic chemotherapy treatment.
2; Patients with LTBI recently diagnosed not following any prophylactic chemotherapy treatment.
3; Patients with LTBI diagnosed time ago.
4; Positive control for the Exhaled Breath condensate assay only. Patients with active TB will conform this group. The n of this group is determined, as it will only be used as a positive control to prove the bacilli's DNA can be detected in the exhaled breath condensate.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
QuantiFeron-Gold-In Tube method assay	Every 6 months during 3 years
Detection of M.tuberculosis DNA and RNA in the exhaled breath condensate	Once every year (every 6 months if possible), during 3 years

Collaborators and Investigators

• Sponsor: Germans Trias i Pujol Hospital
• Collaborators: Fondo de Investigacion Sanitaria
• Investigators: Principal Investigator: Pere-Joan Cardona, MD, PhD, Fundació Institut Germans Trias i Pujol

Publications and helpful links

General Publications

• Cardona PJ. A dynamic reinfection hypothesis of latent tuberculosis infection. Infection. 2009 Apr;37(2):80-6. doi: 10.1007/s15010-008-8087-y. Epub 2009 Mar 23.
• Caceres N, Tapia G, Ojanguren I, Altare F, Gil O, Pinto S, Vilaplana C, Cardona PJ. Evolution of foamy macrophages in the pulmonary granulomas of experimental tuberculosis models. Tuberculosis (Edinb). 2009 Mar;89(2):175-82. doi: 10.1016/j.tube.2008.11.001. Epub 2008 Dec 24.
• Cardona PJ. New insights on the nature of latent tuberculosis infection and its treatment. Inflamm Allergy Drug Targets. 2007 Mar;6(1):27-39. doi: 10.2174/187152807780077282.
• Mack U, Migliori GB, Sester M, Rieder HL, Ehlers S, Goletti D, Bossink A, Magdorf K, Holscher C, Kampmann B, Arend SM, Detjen A, Bothamley G, Zellweger JP, Milburn H, Diel R, Ravn P, Cobelens F, Cardona PJ, Kan B, Solovic I, Duarte R, Cirillo DM; C. Lange; TBNET. LTBI: latent tuberculosis infection or lasting immune responses to M. tuberculosis? A TBNET consensus statement. Eur Respir J. 2009 May;33(5):956-73. doi: 10.1183/09031936.00120908.

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Anticipated): December 1, 2011
• Study Completion (Anticipated): December 1, 2011

Study Registration Dates

• First Submitted: May 19, 2009
• First Submitted That Met QC Criteria: May 19, 2009
• First Posted (Estimate): May 21, 2009

Study Record Updates

• Last Update Posted (Estimate): July 11, 2011
• Last Update Submitted That Met QC Criteria: July 8, 2011
• Last Verified: November 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Latent Infection; Infections; Communicable Diseases; Tuberculosis; Latent Tuberculosis
• Other Study ID Numbers: HYPDYN; CEIC EO-07-033