Quality assessment of an interferon-gamma release assay for tuberculosis infection in a resource-limited setting.
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.
Hang
Nguyen T L
NT
IMCJ-BMH Medical Collaboration Center, Bach Mai Hospital, Hanoi, Viet Nam. lehang0310@gmail.com
Ishizuka
Naoki
N
Keicho
Naoto
N
Hong
Le T
LT
Tam
Do B
DB
Thu
Vu T X
VT
Matsushita
Ikumi
I
Harada
Nobuyuki
N
Higuchi
Kazue
K
Sakurada
Shinsaku
S
Lien
Luu T
LT
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
D000942:Antigens, Bacterial; D007371:Interferon-gamma