title: Common severe infections in chronic granulomatous disease.
abstract: BACKGROUND
  Chronic granulomatous disease (CGD) is due to defective nicotinamide adenine dinucleotide phosphate oxidase activity and characterized by recurrent infections with a limited spectrum of bacteria and fungi as well as inflammatory complications. To understand the impact of common severe infections in CGD, we examined the records of 268 patients followed at a single center over 4 decades.
  
  
  METHODS
  All patients had confirmed diagnoses of CGD, and genotype was determined where possible. Medical records were excerpted into a standard format. Microbiologic analyses were restricted to Staphylococcus, Burkholderia, Serratia, Nocardia, and Aspergillus.
  
  
  RESULTS
  Aspergillus incidence was estimated at 2.6 cases per 100 patient-years; Burkholderia, 1.06 per 100 patient-years; Nocardia, 0.81 per 100 patient-years; Serratia, 0.98 per 100 patient-years, and severe Staphylococcus infection, 1.44 per 100 patient-years. Lung infection occurred in 87% of patients, whereas liver abscess occurred in 32%. Aspergillus incidence was 55% in the lower superoxide-producing quartiles (quartiles 1 and 2) but only 41% in the higher quartiles (rate ratio, <0.0001). Aspergillus and Serratia were somewhat more common in lower superoxide producing gp91phox deficiency. The median age at death has increased from 15.53 years before 1990 to 28.12 years in the last decade. Fungal infection carried a higher risk of mortality than bacterial infection and was the most common cause of death (55%). Gastrointestinal complications were not associated with either infection or mortality.
  
  
  CONCLUSIONS
  Fungal infections remain a major determinant of survival in CGD. X-linked patients generally had more severe disease, and this was generally in those with lower residual superoxide production. Survival in CGD has increased over the years, but infections are still major causes of morbidity and mortality.
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda.
authors.forename: Beatriz E
authors.initials: BE
authors.lastname: Marciano
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda.
authors.forename: Christine
authors.initials: C
authors.lastname: Spalding
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda.
authors.forename: Alan
authors.initials: A
authors.lastname: Fitzgerald
authors.affiliation: Clinical Research Directorate/Clinical Monitoring Research Program.
authors.forename: Daphne
authors.initials: D
authors.lastname: Mann
authors.affiliation: Clinical Research Directorate/Clinical Monitoring Research Program.
authors.forename: Thomas
authors.initials: T
authors.lastname: Brown
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda.
authors.forename: Sharon
authors.initials: S
authors.lastname: Osgood
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda.
authors.forename: Lynne
authors.initials: L
authors.lastname: Yockey
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda.
authors.forename: Dirk N
authors.initials: DN
authors.lastname: Darnell
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda.
authors.forename: Lisa
authors.initials: L
authors.lastname: Barnhart
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda.
authors.forename: Janine
authors.initials: J
authors.lastname: Daub
authors.affiliation: Clinical Research Directorate/Clinical Monitoring Research Program.
authors.forename: Lisa
authors.initials: L
authors.lastname: Boris
authors.affiliation: Clinical Research Directorate/Clinical Monitoring Research Program.
authors.forename: Amy P
authors.initials: AP
authors.lastname: Rump
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Anderson
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda.
authors.forename: Carissa
authors.initials: C
authors.lastname: Haney
authors.affiliation: Clinical Services Program, Applied Developmental Research Directorate, Leidos Biomedical Research, Inc, Frederick National Laboratory for Cancer Research.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Kuhns
authors.affiliation: Department of Laboratory Medicine, NIH Clinical Center, Bethesda.
authors.forename: Sergio D
authors.initials: SD
authors.lastname: Rosenzweig
authors.affiliation: Laboratory of Host Defenses, National Institute for Allergy and Infectious Diseases, NIH, Rockville.
authors.forename: Corin
authors.initials: C
authors.lastname: Kelly
authors.affiliation: Department of Laboratory Medicine, NIH Clinical Center, Bethesda.
authors.forename: Adrian
authors.initials: A
authors.lastname: Zelazny
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda.
authors.forename: Tamika
authors.initials: T
authors.lastname: Mason
authors.affiliation: Laboratory of Host Defenses, National Institute for Allergy and Infectious Diseases, NIH, Rockville.
authors.forename: Suk See
authors.initials: SS
authors.lastname: DeRavin
authors.affiliation: Laboratory of Host Defenses, National Institute for Allergy and Infectious Diseases, NIH, Rockville.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kang
authors.affiliation: Laboratory of Host Defenses, National Institute for Allergy and Infectious Diseases, NIH, Rockville.
authors.forename: John I
authors.initials: JI
authors.lastname: Gallin
authors.affiliation: Department of Laboratory Medicine, NIH Clinical Center, Bethesda.
authors.forename: Harry L
authors.initials: HL
authors.lastname: Malech
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda.
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Olivier
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda.
authors.forename: Gulbu
authors.initials: G
authors.lastname: Uzel
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda.
authors.forename: Alexandra F
authors.initials: AF
authors.lastname: Freeman
authors.affiliation: Liver Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland.
authors.forename: Theo
authors.initials: T
authors.lastname: Heller
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda.
authors.forename: Christa S
authors.initials: CS
authors.lastname: Zerbe
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
mesh_terms: D000293:Adolescent; D000328:Adult; D001228:Aspergillosis / Q000453:epidemiology*; D001424:Bacterial Infections / Q000453:epidemiology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016019:Survival Analysis; D055815:Young Adult
keywords: CGD; bacterial infection; fungal infection; superoxide production; survival