Natural History of Individuals With Immune System Problems That Lead to Fungal Infections

May 28, 2026 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

The Natural History and Pathogenesis of Human Fungal Infections

Background:

- The immune system is made up of special cells, tissues, and organs that fight infections. Problems with this system may lead to frequent, severe, or unusual fungal infections. These infections are often difficult to treat. Researchers want to collect blood and tissue samples from people who have unusual, persistent or severe fungal infections or immune problems that increase the risk of these infections.

Objectives:

- To collect medical information and samples for a long-term study of people with immune system problems that lead to fungal infections.

Eligibility:

  • People with a history of fungal infections caused by immune system problems.
  • Parents, children, and siblings of this group.
  • Healthy volunteers not related to the first two groups.

Design:

  • This long-term study may last for up to 25 years. Those in the study may need to provide new information about every 6 months. The procedures for each person may vary with the particular diagnosis and the extent of fungal infection. Healthy volunteers may have only one or two visits.
  • At the first visit, those in the study will have a full medical history and physical exam. They will also provide blood.
  • Research procedures may include the following:
  • Saliva, urine or stool testing
  • Mouthwash collection for DNA testing
  • Collection of cheek cells, nail clippings, or vaginal fluid
  • Tests of leftover tissue or body fluid from previous medical procedures
  • Skin or oral mucous membrane biopsy
  • Collection of white blood cells
  • Followup visits will involve a physical exam and updated medical history. Blood, saliva, urine, or nail clipping samples may be taken for ongoing studies. Any additional tests or exams required by the study doctors may also be done.
  • Participants may withdraw from the study pool at any time.

Study Overview

Status

Recruiting

Conditions

Detailed Description

This protocol is a natural history study designed to investigate the clinical, microbiologic, genetic and immunologic correlates of primary immune deficiencies and other conditions associated with mucocutaneous and invasive fungal infections (IFIs). The hypothesis is that chronic mucocutaneous mycoses and IFIs are caused by abnormalities in immune function in these patients that can be identified using modern methods in molecular and cell biology and immunology. For inclusion, patients must have a history of or an active mucocutaneous or invasive fungal infection, but may or may not have a defined primary or acquired immunodeficiency state. Patients will undergo evaluations that include history/physical examination and blood, saliva, and possible tissue sampling for genetic and immunological testing. Patient relatives may also be screened for clinical, microbiological, genetic and/or immunological correlates of host defense abnormalities. Healthy volunteers will be enrolled as a source of control blood, saliva, and possible tissue sampling, and for genetic testing.

The aim of this protocol is to use modern methods in molecular and cell biology and immunology to elucidate the immunopathogenesis of fungal disease in humans. A better understanding of primary immunodeficiency and identification of fungal and host risk factors for fungal infection may provide new insights into pathogenesis and identify targets for development of novel therapies. Enrolled subjects may be followed for up to 25 years to undergo additional clinical evaluation and sampling. Follow-up may occur every 6 months or more frequently depending on clinical course, the underlying risk factor(s), and the type of fungal infection. Under some circumstances, standard medical treatment will be provided for a fungal infection or immune deficiency.

Study Type

Observational

Enrollment (Estimated)

1200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • Recruiting
        • National Institutes of Health Clinical Center
        • Contact:
          • For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)
          • Phone Number: TTY dial 711 800-411-1222
          • Email: ccopr@nih.gov

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 day to 99 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

The study population will be drawn from referrals from the NIH Clinical Center staff, physicians at outside medical facilities, the Clinical Center Volunteer Program, and self-referrals. Patients may be evaluated as inpatients, or at the NIAID outpatient clinic depending on the severity of the clinical manifestations of their infection. The patients genetic relatives will be evaluated at the NIAID outpatient clinic. Patients or relatives who meet the inclusion and/or exclusion criteria, but who are not able to travel to the NIH Clinical Center may be enrolled in the study and evaluated for immune and genetic defects using send-in blood samples or clinical specimens (e.g., previously obtained biopsy specimens or saliva). Healthy volunteers must be seen at NIH and will not have the option to mail in samples.

Description

  • INCLUSION CRITERIA:

Patients:

Patients with or without inherited or acquired abnormalities of immune function manifesting mucocutaneous and/or invasive fungal infections are eligible for screening and assessment under this protocol. Specifically, patients must meet all the following inclusion criteria in order to participate in this study:

Adults or children (regardless of age, sex, or ethnicity/race) with a known or yet uncharacterized inherited immunodeficiency and a definitively diagnosed mucocutaneous or invasive fungal infection.

OR

Adults or children (regardless of age, sex, or ethnicity/race) with acquired immunodeficiency and a severe, unusual, persistent or treatment-refractory chronic mucocutaneous fungal infection.

OR

Adults or children (regardless of age, sex, or ethnicity/race) with acquired immunodeficiency and a possible, probable or proven invasive fungal infection (European Organization for Research and Treatment of Cancer / Mycoses Study Group criteria).

OR

Adults or children (regardless of age, sex, or ethnicity/race) with a well-documented prior, unusual, severe, persistent, or treatment-refractory mucocutaneous or invasive fungal infection(s), who have clinically recovered from the fungal infection.

OR

Adults or children (regardless of age, sex, or ethnicity/race) with confirmed or suspected autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) who have not yet developed CMC.

Ongoing care by a referring/primary care physician (inside or outside NIH).

Willing to allow storage of blood and tissue samples for future analyses.

Willing to allow genetic testing from blood, body fluids or tissue specimens.

Willing to have HIV testing

Able to provide informed consent or be accompanied by a parent(s)/legal guardian(s) or legally authorized representative (LAR) who is able to provide informed consent.

No children under the age of 2 years will be seen at the Clinical Center, however they will be able to participate via mail-in specimens

Patient Relatives:

Individuals (regardless of age, sex, or ethnicity/race) who are genetically related to the patient (e.g., mother, father, siblings, children) may be recruited to establish the genetic origin of immune defects that may be identified in the study patients at the discretion of the PI. Relatives must meet all the following inclusion criteria in order to participate in this study:

Willing to allow storage of blood and tissue samples for future analyses.

Willing to allow genetic testing from blood, body fluids or tissue specimens.

Willing to have HIV testing

Able to provide informed consent or, if younger than 18, be accompanied by a parent(s)/legal guardian(s) who is able to provide informed consent.

Healthy Volunteers:

Healthy adults regardless of sex, and ethnicity/race between the ages of 18 and 85 years old may be eligible to participate in this study. Healthy volunteers must meet all the following inclusion criteria in order to participate in this study:

Willing to allow storage of blood and tissue samples for future analyses.

Willing to allow genetic testing from blood, body fluids or tissue specimens.

Willing to have HIV testing

Able to provide informed consent

NIH employees are eligible

EXCLUSION CRITERIA:

Patients:

A patient will not be eligible if he/she has any of the following:

Any condition which, in the investigator's opinion, may interfere with the evaluation of a co-existing abnormality of immunity that is the subject of study under this protocol.

Any condition which, in the investigator's opinion, places the patient at undue risk by participating in the study.

Unwillingness to undergo testing or procedures associated with this protocol.

Hemoglobin of < 7 gm/dL. If a patient is enrolled solely to obtain left-over pathology specimens, saliva, a buccal sample, skin swab, vaginal swab, or a stool sample, this exclusion criteria will not apply as there will be no blood withdrawal.

Patient Relatives:

A genetically related relative will not be eligible for this study if he/she has any condition which, in the investigator's opinion, may interfere with the evaluation of an immune system abnormality that is the subject of study under this protocol.

Healthy Volunteers:

A healthy volunteer will not be eligible if he/she has any of the following:

HIV infection.

History of recurrent or severe infections.

History of an underlying malignancy or receipt of cancer chemotherapy within the past 5 years

Receipt of systemic corticosteroids or other systemic immunosuppressants or immunomodulators within the past 30 days

Pregnancy or lactating

History of heart, lung, kidney disease, or bleeding disorders.

Any condition which, in the investigator's opinion, may interfere with the comparison of clinical specimens against those obtained from affected subjects.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Fungal infections
Patients with or without inherited or acquired abnormalities of immune function manifesting mucocutaneous and/or invasive fungal infections

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Immunological mechanisms of fungal susceptibility
Time Frame: 25 years
Characterize and understand the immunological mechanism(s) by which inherited immunodeficiencies or acquired conditions increase susceptibility to mucocutaneous and invasive fungal infections.
25 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine microbiologic test usefullness
Time Frame: 25 years
Determine the usefulness of various microbiologic tests (e.g., cultures, serology, molecular assays) for diagnosis and follow-up of the course of fungal infections.
25 years
Determine immunological profile of mucosal fungal infections
Time Frame: 25 years
Define the transcriptional profiles and perform proteomic and microbiome analyses of skin, oral and/or vaginal mucosa, and/or other tissues, and body fluids of patients with inherited or acquired conditions predisposing them to fungal infections.
25 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Principal Investigator: Michail S Lionakis, M.D., National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 5, 2012

Study Registration Dates

First Submitted

June 30, 2011

First Submitted That Met QC Criteria

June 30, 2011

First Posted (Estimated)

July 1, 2011

Study Record Updates

Last Update Posted (Actual)

May 29, 2026

Last Update Submitted That Met QC Criteria

May 28, 2026

Last Verified

April 23, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 110187
  • 11-I-0187

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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