Mycobacterial and Opportunistic Infections in HIV-Negative Thai and Taiwanese Patients Associated With Autoantibodies to Interferon-gamma

NCT00814827 | Active Not Recruiting

• 2 other identifiers: 99990906009-I-N060
• Study Type: observational
• Target: 224
• Locations: 3 countries
• Sites: 5

Brief Summary

Opportunistic infections are caused by bacteria, mycobacteria, fungi or viruses that do not normally cause infections in people with healthy immune systems. Some of these infections can cause public health concerns, especially in areas with limited access to treatment. People who acquire opportunistic infections usually have diseases that affect their immune systems, such as human immunodeficiency virus (HIV), or do not have enough white blood cells to fight the infection. However, some people acquire opportunistic infections even though they have normal amounts of white blood cells and are free from known diseases that harm their immune systems. This study will investigate some of the reasons that otherwise healthy people get opportunistic infections to learn more about why some people are more likely to have them. This study will include up to 210 HIV-negative males and females older than 18 years of age who have opportunistic infections. The patients will be drawn from multiple sites in Thailand and Taiwan including Khon Kaen University Hospital, Siriraj Hospital, Ramathibodi Hospital, National Taiwan University Hospital, National Cheng-Kung University Hospital Patients will undergo an initial evaluation that will include a physical examination, medical history, and blood and urine testing. Additional tests will be conducted if the researchers consider that the tests are medically necessary to treat the opportunistic infection; the results of the tests will be reviewed and saved for study purposes. Depending on the severity of the infection, the initial evaluation may take more than 1 day to complete. After the evaluation, patients will be given standard and appropriate medicines to treat the infections. Patients will return for follow-up visits to allow researchers to monitor their condition and to assess how well the patient is responding to the treatment. Patients will be evaluated by the study researchers at least once a year for 2 years following the initial treatment.

Conditions

Nontuberculous Mycobacteria; Mycobacterium Tuberculosis; Opportunistic Infections

Keywords

Interferon-Gamma; Autoantibodies; Disseminated Infection; Pulmonary Infection; Blood Donor; Natural History

Outcome Measures

Primary Outcomes (1)

• Identification of the presence of autoantibodies to IFNy in HIV-negative Thai and Taiwanese patients with disseminated NTM and OI who are followed at the participating institutions.

  Compare the baseline prevalence rate of autoantibodies to IFNg, as defined by having \>75% inhibition, in patients with disseminated NTM or other OI (groups 1 and 2) versus normal or diseased controls (groups 3 and 5).

  ongoing

Secondary Outcomes (3)

• Identification of predisposing factors for the development of autoimmunity to cytokines and/or their receptors.

  ongoing

• Identification of other autoantibodies that might manifest similarly to patients with autoantibodies to IFNg.

  ongoing

• Characterization of the natural history and specific microbiology in HIV-negative patients with disseminated NTM and other OI and to determine any statistically significant differences from MTB controls or healthy blood bank donors.

  ongoing

Study Arms (5)

Group 1

Patients with nontuberculous mycobacteria (NTM) alone.

Group 2

Patients with non-NTM opportunistic infection, either with or without concurrent NTM infection.

Group 3

Patients with pulmonary mycobacterium tuberculosis (MTB).

Group 4

Patients with disseminated mycobacterium tuberculosis (MTB).

Group 5

Blood Specimen Donors.

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This is a prospective natural history cohort study with a case-control component. Patients will be recruited from 5 groups: 1) subjects with NTM alone, 2) subjects with a non-NTM OI, either with or without concurrent NTM infection, 3) subjects with pulmonary MTB, 4) subjects with disseminated MTB, and 5) Blood Specimen Donor controls.

You may qualify if:

• Patients must meet all of the following criteria at the time of evaluation to be eligible for enrollment into the study cohorts:
• Group 1 (NTM alone):
• Past or current infection with NTM proven by culture or specific DNA detection in the presence of a compatible clinical picture as judged by the responsible clinician and PI on site.
• NTM is not felt to be iatrogenic (such as indwelling catheter associated or post-operative wound infection)
• HIV negative within 3 months either prior to the diagnosis of OI, or prior to enrollment in this study, if HIV status was unknown at the time of OI
• No evidence of active malignancy
• No systemic corticosteroids at time of diagnosis of OI (defined as greater than 4 weeks at a dose greater than 10 mg per day of prednisone within 3 months prior to diagnosis of the NTM)
• No preexisting immune deficiency
• Group 2 (non-NTM OI with or without NTM):
• Patients must have or have had proven infection with one or more of the following organisms: disseminated Salmonella, Listeria, Penicillium, Burkholderia pseudomallei, Cryptococcus, Histoplasma, Herpes zoster involving 2 or more non-contiguous dermatomes, or extradermal involvement or other opportunistic infections not listed above, but relevant, as determined by the PI.
• Patient may have infection with NTM in addition to one or more of the above infection(s).
• HIV-negative within 3 months either prior to the diagnosis of OI, or prior to enrollment in this study, if HIV status was unknown at the time of OI diagnosis
• No evidence of active malignancy
• No systemic corticosteroids at time of diagnosis of OI (defined as greater than 4 weeks at a dose greater than 10 mg per day of prednisone within 3 months prior to diagnosis of the NTM)
• No preexisting immune deficiency

You may not qualify if:

• Patients will be excluded for the following reasons:
• HIV-positive serostatus for groups 1, 2 and 4 (groups 3 and 5 we will not be routinely performing HIV testing)
• Active malignancy
• Medical conditions requiring immune modulating therapy (i.e. corticosteroids, biological agents, anti-metabolites) and /or chemotherapy
• Any other medical conditions unsuitable for this study as determined by the principal investigator
• Age less than 18 years
• Subjects cannot be receiving any other investigational study agents when enrolling on this study.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (5)

National Taiwan University

Taiwan, China

Location

National Cheng Kung University

Tainan, Taiwan

Location

National Siriraj Hospital, Mahidol Universtiy

Bangkok, Thailand

Location

Ramathibodi Hospital, Mahidol Universtiy

Bangkok, Thailand

Location

Srinagarind Hospital

Khon Kaen, 40002, Thailand

Location

Related Publications (4)

• Dorman SE, Holland SM. Interferon-gamma and interleukin-12 pathway defects and human disease. Cytokine Growth Factor Rev. 2000 Dec;11(4):321-33. doi: 10.1016/s1359-6101(00)00010-1.

  PMID: 10959079 BACKGROUND

• Patel SY, Ding L, Brown MR, Lantz L, Gay T, Cohen S, Martyak LA, Kubak B, Holland SM. Anti-IFN-gamma autoantibodies in disseminated nontuberculous mycobacterial infections. J Immunol. 2005 Oct 1;175(7):4769-76. doi: 10.4049/jimmunol.175.7.4769.

  PMID: 16177125 BACKGROUND

• Kampmann B, Hemingway C, Stephens A, Davidson R, Goodsall A, Anderson S, Nicol M, Scholvinck E, Relman D, Waddell S, Langford P, Sheehan B, Semple L, Wilkinson KA, Wilkinson RJ, Ress S, Hibberd M, Levin M. Acquired predisposition to mycobacterial disease due to autoantibodies to IFN-gamma. J Clin Invest. 2005 Sep;115(9):2480-8. doi: 10.1172/JCI19316. Epub 2005 Aug 25.

  PMID: 16127458 BACKGROUND

• Browne SK, Burbelo PD, Chetchotisakd P, Suputtamongkol Y, Kiertiburanakul S, Shaw PA, Kirk JL, Jutivorakool K, Zaman R, Ding L, Hsu AP, Patel SY, Olivier KN, Lulitanond V, Mootsikapun P, Anunnatsiri S, Angkasekwinai N, Sathapatayavongs B, Hsueh PR, Shieh CC, Brown MR, Thongnoppakhun W, Claypool R, Sampaio EP, Thepthai C, Waywa D, Dacombe C, Reizes Y, Zelazny AM, Saleeb P, Rosen LB, Mo A, Iadarola M, Holland SM. Adult-onset immunodeficiency in Thailand and Taiwan. N Engl J Med. 2012 Aug 23;367(8):725-34. doi: 10.1056/NEJMoa1111160.

  PMID: 22913682 DERIVED

MeSH Terms

Conditions

Opportunistic Infections

Condition Hierarchy (Ancestors)

Infections

Study Officials

• Christa S Zerbe, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 24, 2008
• First Posted: December 25, 2008
• Study Start: January 7, 2010
• Last Updated: May 5, 2026

Record last verified: 2026-04-16

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP
• Time Frame: IPD and supporting information will be available after completion of the study.
• Access Criteria: Data will be shared through:@@@@@@@@@@@@ (Summation)BTRIS (automatic for activities in the NIH CC).@@@@@@@@@@@@ (Summation)Approved outside collaborators under appropriate individual agreements.@@@@@@@@@@@@ (Summation)Publication and/or public presentations.@@@@@@@@@@@@Data might be shared before publication.@@@@@@@@@@@@The PI will review all requests for sharing data.

Locations

TW (1); TH (3); CN (1)