title: Disseminated tuberculosis in human immunodeficiency virus infection: ineffective immunity, polyclonal disease and high mortality.
abstract: BACKGROUND
  Disseminated tuberculosis (TB) is a major cause of death in patients with the acquired immune-deficiency syndrome (AIDS), but its pathogenesis and clinical features have not been defined prospectively.
  
  
  METHODS
  Human immunodeficiency virus (HIV) infected adults with a CD4 count ≥ 200 cells/μl and bacille Calmette-Guérin scar underwent immunologic evaluation and subsequent follow-up.
  
  
  RESULTS
  Among 20 subjects who developed disseminated TB, baseline tuberculin skin tests were ≥15 mm in 14 (70%) and lymphocyte proliferative responses to Mycobacterium tuberculosis were positive in 14 (70%). At the time of diagnosis, fever ≥2 weeks plus ≥5 kg weight loss was reported in 16 (80%) patients, abnormal chest X-rays in 7/17 (41%), and positive sputum cultures in 10 (50%); median CD4 count was 30 cells/μl (range 1-122). By insertion sequence (IS) 6110 analysis, 14 (70%) blood isolates were clustered and 3/8 (37%) concurrent sputum isolates represented a different strain (polyclonal disease). Empiric TB treatment was given to eight (40%) patients; 11 (55%) died within a month.
  
  
  CONCLUSIONS
  Disseminated TB in HIV occurs with cellular immune responses indicating prior mycobacterial infection, and IS6110 analysis suggests an often lethal combination of reactivation and newly acquired infection. Control will require effective prevention of both remotely and recently acquired infection, and wider use of empiric therapy in patients with advanced AIDS and prolonged fever.
authors: Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA. fvr@dartmouth.edu
authors: C F
authors: CF
authors: von Reyn
authors: S
authors: S
authors: Kimambo
authors: L
authors: L
authors: Mtei
authors: R D
authors: RD
authors: Arbeit
authors: I
authors: I
authors: Maro
authors: M
authors: M
authors: Bakari
authors: M
authors: M
authors: Matee
authors: T
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authors: Lahey
authors: L V
authors: LV
authors: Adams
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authors: Black
authors: T
authors: T
authors: Mackenzie
authors: J
authors: J
authors: Lyimo
authors: S
authors: S
authors: Tvaroha
authors: R
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authors: Waddell
authors: B
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authors: Kreiswirth
authors: C R
authors: CR
authors: Horsburgh
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authors: Pallangyo
mesh_terms: D000328:Adult; D001500:BCG Vaccine / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D049109:Cell Proliferation; D016009:Chi-Square Distribution; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000175:diagnosis / Q000276:immunology / Q000401:mortality*; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology / Q000382:microbiology; D008297:Male; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity; D011379:Prognosis; D011446:Prospective Studies; D013902:Radiography, Thoracic; D013183:Sputum / Q000382:microbiology; D013636:Tanzania / Q000453:epidemiology; D013997:Time Factors; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis / Q000276:immunology / Q000382:microbiology / Q000401:mortality* / Q000517:prevention & control*
chemical_list: D001500:BCG Vaccine; D007371:Interferon-gamma