Quality assessment of an interferon-gamma release assay for tuberculosis infection in a resource-limited setting
1 IMCJ-BMH Medical Collaboration Center, Bach Mai Hospital, Hanoi, Viet Nam
2 International Medical Center of Japan, Research Institute, Tokyo, Japan
3 Hanoi Tuberculosis and Lung Disease Hospital, Hanoi, Viet Nam
4 Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan
BMC Infectious Diseases 2009, 9:66 doi:10.1186/1471-2334-9-66Published: 18 May 2009
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.
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.
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.
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.