title: Quality assessment of an interferon-gamma release assay for tuberculosis infection in a resource-limited setting.
abstract: BACKGROUND
  When a test for diagnosis of infectious diseases is introduced in a resource-limited setting, monitoring quality is a major concern. An optimized design of experiment and statistical models are required for this assessment.
  
  
  METHODS
  Interferon-gamma release assay to detect tuberculosis (TB) infection from whole blood was tested in Hanoi, Viet Nam. Balanced incomplete block design (BIBD) was planned and fixed-effect models with heterogeneous error variance were used for analysis. In the first trial, the whole blood from 12 donors was incubated with nil, TB-specific antigens or mitogen. In 72 measurements, two laboratory members exchanged their roles in harvesting plasma and testing for interferon-gamma release using enzyme linked immunosorbent assay (ELISA) technique. After intervention including checkup of all steps and standard operation procedures, the second trial was implemented in a similar manner.
  
  
  RESULTS
  The lack of precision in the first trial was clearly demonstrated. Large within-individual error was significantly affected by both harvester and ELISA operator, indicating that both of the steps had problems. After the intervention, overall within-individual error was significantly reduced (P < 0.0001) and error variance was no longer affected by laboratory personnel in charge, indicating that a marked improvement could be objectively observed.
  
  
  CONCLUSIONS
  BIBD and analysis of fixed-effect models with heterogeneous variance are suitable and useful for objective and individualized assessment of proficiency in a multistep diagnostic test for infectious diseases in a resource-constrained laboratory. The action plan based on our findings would be worth considering when monitoring for internal quality control is difficult on site.
authors.affiliation: IMCJ-BMH Medical Collaboration Center, Bach Mai Hospital, Hanoi, Viet Nam. lehang0310@gmail.com
authors.forename: Nguyen T L
authors.initials: NT
authors.lastname: Hang
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishizuka
authors.forename: Naoto
authors.initials: N
authors.lastname: Keicho
authors.forename: Le T
authors.initials: LT
authors.lastname: Hong
authors.forename: Do B
authors.initials: DB
authors.lastname: Tam
authors.forename: Vu T X
authors.initials: VT
authors.lastname: Thu
authors.forename: Ikumi
authors.initials: I
authors.lastname: Matsushita
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Harada
authors.forename: Kazue
authors.initials: K
authors.lastname: Higuchi
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Sakurada
authors.forename: Luu T
authors.initials: LT
authors.lastname: Lien
mesh_terms: D000704:Analysis of Variance; D000942:Antigens, Bacterial; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D007755:Laboratories, Hospital / Q000592:standards; D017056:Medical Laboratory Personnel / Q000193:education; D015233:Models, Statistical; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification*; D011786:Quality Control; D014376:Tuberculosis / Q000175:diagnosis*; D014744:Vietnam
chemical_list: D000942:Antigens, Bacterial; D007371:Interferon-gamma