Fungal Infection Susceptibility

NCT00001352 | Recruiting

• 2 other identifiers: 93010693-I-0106
• Study Type: observational
• Target: 800
• Locations: 1 country
• Sites: 1

Brief Summary

The protocol will be carried out in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) and the following United States Code of Federal Regulations (CFR) applicable to clinical studies: 45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812. NIH-funded investigators and study site staff who are responsible for the conduct, management, or oversight of NIH-funded studies have completed Human Subjects Protection and ICH GCP Training. The protocol, informed consent form(s), recruitment materials, and all participant materials will be submitted to the Institutional Review Board (IRB) for review and approval. Approval of both the protocol and the consent form must be obtained before any participant is enrolled. Any amendment to the protocol will require review and approval by the IRB before the changes are implemented to the study. In addition, all changes to the consent form will be approved by the IRB; an IRB determination will be made regarding whether a new consent needs to be obtained from participants who provided consent, using a previously approved consent form.

Conditions

Cryptococcal Pneumonia; Cryptococcal Meningitis; Pulmonary Cryptococcosis; Cryptococcosis; Cryptococcal Infection

Keywords

Natural History; Cryptococcus; Cryptococcus Neoformans; Cryptococcus gattii

Outcome Measures

Primary Outcomes (1)

• Characterize the full spectrum of clinical disease of Cryptococcosis in previously healthy adults without known immune predisposition.

  1-5 years

Secondary Outcomes (3)

• Characterize the immunological and genetic mechanisms predisposing to disease acquisition.

  1-5 years

• Understand the inflammatory response and distinguish its consequences from those directly due to fungal growth.

  1-5 years

• Understand the natural history of disease progression or regression over time.

  1-5 years

Study Arms (3)

Blood Relatives

Will be placed in a control group. Must be a blood relative of a patient enrolled in the study. Participant age must be 18 years or older. Relatives may be excluded if they have a condition that may interfere with evaluation of an immune system abnormality.

Healthy Volunteers

Will be placed in a control group. Participant age must be 18 years or older. Healthy volunteers will be excluded if they have HIV, viral hepatitis (B or C), history of recurrent or severe infections, history of intravenous drug use, history of engaging in high-risk activities for HIV exposure, receiving chemotherapeutic agents, immunosuppressants, have underlying malignancies, pregnancy, or a history of heart disease, lung disease, kidney disease, or bleeding disorders.

Patient Population

Previously healthy adult patients diagnosed with Cryptococcosis and have no predisposing conditions, such as HIV.

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Study subjects will consist of previously healthy adults without known prior conditions who have cryptococcosis, blood relatives of these patients, and healthy adult volunteers. Potential Cryptococcus patients must be 18 or older with evidence of positive Cryptococcus infection results as shown through their medical records, telephone interviews or referring physician. This includes a positive Cryptococcus culture (neoformans or gattii), a positive cryptococcal antigen from serum or CSF with CSF cell count and chemistry consistent with Cryptococcus infection, or histopathology showing cryptococci. Blood relatives and healthy volunteers must be 18 years or older.

You may qualify if:

• Patients
• Patients must:
• Have cryptococcosis as determined by information collected from their medical records, telephone interviews, or from a referring physician:
• histopathology showing cryptococci; or
• culture of C. neoformans or C. gattii
• a positive cryptococcal antigen in the serum and/or CSF, together with CSF cell count and chemistry consistent with cryptococcal meningitis.
• Be over the age of 18 years old.
• Have a primary physician outside of the NIH.
• Agree to undergo genetic testing that will include WES and high density SNP arrays as appropriate for possible WES linkage studies.
• Allow samples to be stored for future research.
• Pregnant patients will not be excluded. However, research procedures greater than minimal risk including bone marrow biopsy and apheresis would not be performed on pregnant subjects. Otherwise, pregnant patients with cryptococcus would be treated with as per standard of care, minimizing teratogenic potential of drugs and ionizing radiation whenever possible.
• Blood Relatives of Patients
• Blood relatives must:
• Be a genetic relative of a patient enrolled in this study
• Be over the age of 18 years old

You may not qualify if:

• Patients
• Patients will be excluded for any of the following:
• The presence of certain types of acquired abnormalities of immunity due to:
• HIV
• Cancer chemotherapeutic agent(s)
• Monoclonal antibody therapy directed against a patient s immune system
• Any condition that in the opinion of the investigator may interfere with the evaluation of a co-existing abnormality of immunity that is the subject of study under this protocol. For example, we may exclude patients with Cushing s disease that have very high cortisol levels at the time of diagnosis of their cryptococcosis.
• Genetic Relatives of Patients
• Genetic relatives will be excluded for the following:
• Any condition that in the opinion of the investigator may interfere with evaluation of an immune system abnormality that is the subject of study under this protocol.
• Healthy Volunteers
• Healthy volunteers will be excluded for any of the following:
• HIV or viral hepatitis (B or C).
• History of recurrent or severe infections.
• History of intravenous drug use.

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (15)

• Baddley JW, Forrest GN; AST Infectious Diseases Community of Practice. Cryptococcosis in solid organ transplantation. Am J Transplant. 2013 Mar;13 Suppl 4:242-9. doi: 10.1111/ajt.12116. No abstract available.

  PMID: 23465017 BACKGROUND

• Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS. 2009 Feb 20;23(4):525-30. doi: 10.1097/QAD.0b013e328322ffac.

  PMID: 19182676 BACKGROUND

• Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ, Harrison TS, Larsen RA, Lortholary O, Nguyen MH, Pappas PG, Powderly WG, Singh N, Sobel JD, Sorrell TC. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2010 Feb 1;50(3):291-322. doi: 10.1086/649858.

  PMID: 20047480 BACKGROUND

• Brizendine KD, Baddley JW, Pappas PG. Predictors of mortality and differences in clinical features among patients with Cryptococcosis according to immune status. PLoS One. 2013;8(3):e60431. doi: 10.1371/journal.pone.0060431. Epub 2013 Mar 26.

  PMID: 23555970 BACKGROUND

• Bratton EW, El Husseini N, Chastain CA, Lee MS, Poole C, Sturmer T, Juliano JJ, Weber DJ, Perfect JR. Comparison and temporal trends of three groups with cryptococcosis: HIV-infected, solid organ transplant, and HIV-negative/non-transplant. PLoS One. 2012;7(8):e43582. doi: 10.1371/journal.pone.0043582. Epub 2012 Aug 24.

  PMID: 22937064 BACKGROUND

• Gullo FP, Rossi SA, Sardi Jde C, Teodoro VL, Mendes-Giannini MJ, Fusco-Almeida AM. Cryptococcosis: epidemiology, fungal resistance, and new alternatives for treatment. Eur J Clin Microbiol Infect Dis. 2013 Nov;32(11):1377-91. doi: 10.1007/s10096-013-1915-8. Epub 2013 Jul 4.

  PMID: 24141976 BACKGROUND

• Baddley JW, Perfect JR, Oster RA, Larsen RA, Pankey GA, Henderson H, Haas DW, Kauffman CA, Patel R, Zaas AK, Pappas PG. Pulmonary cryptococcosis in patients without HIV infection: factors associated with disseminated disease. Eur J Clin Microbiol Infect Dis. 2008 Oct;27(10):937-43. doi: 10.1007/s10096-008-0529-z. Epub 2008 May 1.

  PMID: 18449582 BACKGROUND

• Chen SC, Korman TM, Slavin MA, Marriott D, Byth K, Bak N, Currie BJ, Hajkowicz K, Heath CH, Kidd S, McBride WJ, Meyer W, Murray R, Playford EG, Sorrell TC; Australia and New Zealand Mycoses Interest Group (ANZMIG) Cryptococcus Study. Antifungal therapy and management of complications of cryptococcosis due to Cryptococcus gattii. Clin Infect Dis. 2013 Aug;57(4):543-51. doi: 10.1093/cid/cit341. Epub 2013 May 22.

  PMID: 23697747 BACKGROUND

• Pappas PG. Cryptococcal infections in non-HIV-infected patients. Trans Am Clin Climatol Assoc. 2013;124:61-79.

  PMID: 23874010 BACKGROUND

• Meletiadis J, Walsh TJ, Choi EH, Pappas PG, Ennis D, Douglas J, Pankey GA, Larsen RA, Hamill RJ, Chanock S. Study of common functional genetic polymorphisms of FCGR2A, 3A and 3B genes and the risk for cryptococcosis in HIV-uninfected patients. Med Mycol. 2007 Sep;45(6):513-8. doi: 10.1080/13693780701390140.

  PMID: 17710620 BACKGROUND

• Schepelmann K, Muller F, Dichgans J. Cryptococcal meningitis with severe visual and hearing loss and radiculopathy in a patient without immunodeficiency. Mycoses. 1993 Nov-Dec;36(11-12):429-32. doi: 10.1111/j.1439-0507.1993.tb00734.x.

  PMID: 7935577 BACKGROUND

• Rosen LB, Freeman AF, Yang LM, Jutivorakool K, Olivier KN, Angkasekwinai N, Suputtamongkol Y, Bennett JE, Pyrgos V, Williamson PR, Ding L, Holland SM, Browne SK. Anti-GM-CSF autoantibodies in patients with cryptococcal meningitis. J Immunol. 2013 Apr 15;190(8):3959-66. doi: 10.4049/jimmunol.1202526. Epub 2013 Mar 18.

  PMID: 23509356 BACKGROUND

• Rabbani B, Tekin M, Mahdieh N. The promise of whole-exome sequencing in medical genetics. J Hum Genet. 2014 Jan;59(1):5-15. doi: 10.1038/jhg.2013.114. Epub 2013 Nov 7.

  PMID: 24196381 BACKGROUND

• Mullaney JM, Mills RE, Pittard WS, Devine SE. Small insertions and deletions (INDELs) in human genomes. Hum Mol Genet. 2010 Oct 15;19(R2):R131-6. doi: 10.1093/hmg/ddq400. Epub 2010 Sep 21.

  PMID: 20858594 BACKGROUND

• De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, Pappas PG, Maertens J, Lortholary O, Kauffman CA, Denning DW, Patterson TF, Maschmeyer G, Bille J, Dismukes WE, Herbrecht R, Hope WW, Kibbler CC, Kullberg BJ, Marr KA, Munoz P, Odds FC, Perfect JR, Restrepo A, Ruhnke M, Segal BH, Sobel JD, Sorrell TC, Viscoli C, Wingard JR, Zaoutis T, Bennett JE; European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group; National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008 Jun 15;46(12):1813-21. doi: 10.1086/588660.

  PMID: 18462102 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Meningitis, Cryptococcal; Cryptococcosis

Condition Hierarchy (Ancestors)

Meningitis, Fungal; Central Nervous System Fungal Infections; Mycoses; Bacterial Infections and Mycoses; Infections; Central Nervous System Infections; Central Nervous System Diseases; Nervous System Diseases; Meningitis; Neuroinflammatory Diseases

Study Officials

• Peter R Williamson, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Peter R Williamson, M.D.

CONTACT

(301) 443-8339; williamsonpr@mail.nih.gov

Study Design

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

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: April 1, 1993
• Last Updated: April 28, 2026

Record last verified: 2026-03-23

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)