Clinical Trial: Immune Responses to Mycobacterium Tuberculosis (Mtb) in People With Latent Tuberculosis Infection With or Without Concomitant Helminth Infection

Study Status: Terminated
Recruit Status: Terminated
Study Type: Observational

Official Title: Longitudinal Study of Immune Responses to Mycobacterium Tuberculosis (Mtb) in Subjects With Latent Tuberculosis (TB) Infection(LTBI) With or Without Concomitant Helminth I

Brief Summary:

Background:

Tuberculosis (TB) is a severe disease and a major cause of death in many people worldwide. It is caused by a bacteria that enters through the lungs and can spread elsewhere in the body. People with latent TB have the bacteria that lie dormant but can become active and cause disease. These people are offered treatment to prevent development of active TB. Worldwide, a lot of people with LTBI also have a parasitic worm called a helminth that can stay in the gut or the blood. These parasites can affect the immune system and cause diseases like TB to become worse. Researchers want to see how helminth infection makes it harder for people to fight TB infection.

Objectives:

- To study how the immune system of people with latent tuberculosis infection (LTBI) acts to prevent development of active TB. Also, to study how helminth infection might affect this immune response.

Eligibility:

  • Adults age 18 70 with LTBI as defined by an approved blood test called QuantiFERON TB Gold.
  • No evidence of infections like Hepatitis or HIV
  • Pregnant subjects and subjects taking medications that suppress the immune system are not eligible.
  • Have not received prior treatment for LTBI. Participants might be still eligible if prior treatment for active TB has been received

Design:

Screening phase:

- Participants will be screened with medical history, physical exam, and blood tests for other infections/conditi

Detailed Summary:

Mycobacterium tuberculosis (Mtb) infection remains an important cause of morbidity and mortality worldwide. A problem for eradication efforts is the large reservoir of ~2 billion people with latent tuberculosis (TB) infection (LTBI) and poor understanding of factors leading to active disease progression. Helminth infections geographically overlap with Mtb and induce significant immune-mediated modulation. Although CD4+T cells producing IFN-gamma and TNF-alpha have been implicated in protective immunity to TB, a detailed description of the evolution of protective and immunomodulatory responses in LTBI is lacking. Additionally, there is incomplete understanding of how the immunomodulation caused by helminth co-infection affects such responses.

This protocol will attempt to fill this knowledge gap through comprehensive longitudinal immunological analyses of two populations of subjects with LTBI, with or without concurrent helminth infection (HEL+ and HEL- respectively). In both groups, venipuncture and possibly apheresis will be performed to understand protective and modulatory T cell and monocyte/macrophage responses. Subjects will receive treatment for helminth infection and treatment for LTBI will be offered according to current standard of care guidelines. Two groups of subjects within the LTBI group will be offered bronchoscopy and lavage --- (a) those with structural lung damage from prior treated/healed tuberculosis and (b) those with recent prolonged exposure (greater than or equal to 3 months) to a household contact with active TB.

The primary objective is to evaluate CD4+ T cell responses and regulatory T cell responses in HEL+ and HEL- subjects with LTBI at the time of diagnosis (baseline). HEL+ subjects will then receive treatment for parasitic infection and both groups (HEL+ and HEL-) will be offered LTBI treatme
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Current Primary Outcome: Define the immunologic differences in CD4+ T cell responses between helminth-infected and uninfected subjects with concomitant latent TB at the time of diagnosis and on serial follow-up. [ Time Frame: Pre Treatment for LTBI and pre defined post treatment time points ]

Original Primary Outcome: Define the immunologic differences in CD4+ T cell responses between helminth-infected and uninfected subjects with concomitant latent TB at the time of diagnosis and on serial follow-up [ Time Frame: Pre Treatment for LTBI andpre defined post treatmenttime points ]

Current Secondary Outcome:

  • Evaluate the immune phenotype and functionality of tissue resident immune cells obtained by bronchoalveolar lavage in subjects with LTBI and either: 1) structural lung damage from prior treated/healed pulmonary tuberculosis or 2) recent prolonge... [ Time Frame: Pre Treatment for LTBI and pre defined post treatment time points LTBI and pre definedpost treatment timepoints ]
  • Define the role of stable long lasting antigen-specific IL-2 producing CD4+ central memory T cells in identifying subsets of patients with LTBI [ Time Frame: Pre Treatment for LTBI and pre defined post treatment time points LTBI and pre defined post treatment timepointspoints ]


Original Secondary Outcome:

  • Evaluate the immune phenotype and functionality of tissue resident immune cells obtained by bronchoalveolar lavage in subjects with LTBI and either: 1) structural lung damage from prior treated/healed pulmonary tuberculosis or 2) recent prolonge... [ Time Frame: Pre Treatment forLTBI and pre definedpost treatment timepoints ]
  • Define the role of stable long lasting antigen-specific IL-2 producing CD4+ central memory T cells in identifying subsets of patients with LTBI [ Time Frame: Pre Treatment forLTBI and pre definedpost treatment timepoints ]


Information By: National Institutes of Health Clinical Center (CC)

Dates:
Date Received: August 23, 2014
Date Started: August 15, 2014
Date Completion:
Last Updated: May 12, 2017
Last Verified: May 11, 2017