Immune Responses to Mycobacterium Tuberculosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00340990
Recruitment Status : Completed
First Posted : June 21, 2006
Last Update Posted : February 11, 2019
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Brief Summary:

This study, conducted at the University of Mali in the capital city of Bamako, will investigate how the body reacts to infection with Mycobacterium tuberculosis (MTB), the organism that causes tuberculosis. Tuberculosis is a major global health problem whose solution requires development of an effective vaccine. However, incomplete understanding of how immunity to MTB is acquired and measured limits vaccine development. This study will focus on certain immune system cells - CD4+ T cells - that appear to be very important in fighting tuberculosis.

Individuals 16 years of age and older who have or have not been exposed to either tuberculosis or HIV, or both, may be eligible for this study. Candidates will be screened with a medical history, physical examination, blood tests, review of medical records and laboratory tests, and, if medically indicated, a chest x-ray. Individuals whose medical records indicate a past history of tuberculosis or a positive test for exposure to tuberculosis will have a tuberculin skin test. For this test, a few drops of fluid are placed under the skin to see if the immune system reacts to the substance, indicating previous exposure to MTB.

Participants will come to the University of Mali 10 times over a 1-year period - 7 times within the first 3 months of the study and then once every 3 months until 1 year after enrollment. At each study visit, they will be asked about their medical history and will donate 75 milliliters (about 1/3 cup) of blood, totaling 830 mL over the entire year. More blood may be requested if the participant's immune system reacts strongly to MTB in laboratory tests. No more than 450 mL (2 cups) of blood would be collected every 6 weeks; this amount is the Red Cross limit for regular blood donations every 6 weeks.

The blood samples will be used for tests that measure the level of immunity to tuberculosis. Genetic tests may be performed on blood cells to help interpret special tests of immunity. Because HIV-infected people are included in the study, the findings may also provide information on how HIV renders vulnerability to opportunistic infections, including tuberculosis.

Condition or disease
Mycobacterium Tuberculosis

Detailed Description:
Tuberculosis is a daunting global health problem. The solution requires development of an effective vaccine. But incomplete understanding of Mycobacterium tuberculosis (MTB) immunity-how it is acquired, how it is measured-limits vaccine development to empiric rather than rational approaches. New perspectives are needed. Most individuals infected with MTB never actually develop active tuberculosis. Similarly, most individuals with treated tuberculosis or BCG vaccination are also protected from subsequent disease. These individuals may be said to be immune. One approach to obtaining greater understanding of MTB immunity is to study these individuals to discover mechanisms of immunity that mediate their protection from disease. Because it is already known that CD4+ T cells are a critical component of MTB immunity, studying CD4+ T cell responses to MTB infection in immune individuals is a reasonable starting point. To determine which CD4+ T cell subsets and which CD4+ T cell immune responses are important, we will compare individuals with prior exposure (immunity) to MTB to individuals with active tuberculosis. Because HIV infection interferes with the CD4+ T cell response to MTB, it dramatically increases the risks for acquiring MTB infection and for developing disease. Under these circumstances it is easier to discern mechanisms relevant to MTB immunity because of exaggerated MTB-specific responses. In this study we aim to identify CD4+ T cell subsets and responses that correlate with MTB immunity. We anticipate that these correlations will yield new insight into mechanisms of MTB immunity that will be relevant to vaccine development. In addition, by examining MTB immunity in the setting of HIV coinfection, we anticipate new insights into mechanisms of how HIV causes disease.

Study Type : Observational
Actual Enrollment : 111 participants
Official Title: Pilot Study of CD4+ T Cell Immune Responses to Mycobacterium Tuberculosis
Study Start Date : October 6, 2003
Study Completion Date : November 27, 2015

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Ability to sign informed consent and willingness to comply with study requirements (including storage of blood specimens for future research on HIV, AIDS, MTB or the immune system).


Group A (HIV-/MTB[BCG]) HIV ELISA(2) negative; BCG vaccinated with TST(2) less than 15 mm

Group B (HIV+/MTB[BCG]) HIV ELISA/WB(2) positive; BCG vaccinated with TST less than 5 mm

Group C (HIV-/MTB[pulm]) HIV ELISA negative; pulmonary MTB

Group D (HIV-/MTB[diss]) HIV ELISA negative; disseminated MTB

Group E (HIV+/MTB[pulm]) HIV ELISA/WB positive; pulmonary MTB

Group F (HIV+/MTB[diss]) HIV ELISA/WB positive; disseminated MTB


Age less than 18 years (because of the risk for inducing protocol-related anemia)

Hg less than 7.5 g/dL

Latent MTB infection (as evidenced by a TST greater than 5 mm if HIV infected or greater than 15 mm if HIV uninfected) for arms A and B only.

Past history of treated MTB infection

Known or underlying bleeding disorder (due to risk of bleeding from venipuncture)

Psychiatric illness that might interfere with study compliance

Use of immunomodulators (including corticosteroids and IL-2) or cytotoxic agents (including hydroxyurea) within 45 days of signing consent and at any time during study

Small or difficult to access antecubital veins that make venipuncture difficult

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00340990

University of Mali
Bamako, Mali
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Principal Investigator: Sophia B Siddiqui, M.D. National Institute of Allergy and Infectious Diseases (NIAID)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID) Identifier: NCT00340990     History of Changes
Other Study ID Numbers: 999904009
First Posted: June 21, 2006    Key Record Dates
Last Update Posted: February 11, 2019
Last Verified: November 27, 2015

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
CD4+ T Cell
Lymphocyte Proliferation

Additional relevant MeSH terms:
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections