The Standardization and Control of Serology and Nucleic Acid Testing for Infectious Diseases

Abstract

Historically, the detection of antibodies against infectious disease agents was achieved using test systems that utilized biological functions such as neutralization, complement fixation, hemagglutination, or visualization of binding of antibodies to specific antigens, by testing doubling dilutions of the patient sample to determine an endpoint. These test systems have since been replaced by automated platforms, many of which have been integrated into general medical pathology. Methods employed to standardize and control clinical chemistry testing have been applied to these serology tests. However, there is evidence that these methods are not suitable for infectious disease serology. An overriding reason is that, unlike testing for an inert chemical, testing for specific antibodies to infectious disease agents is highly variable; the measurand for each test system varies in choice of antigen, antibody classes/subclasses, modes of detection, and assay kinetics, and individuals' immune responses vary with time after exposure, individual immune-competency, nutrition, treatment, and exposure to variable circulating sero- or genotypes or organism mutations. Therefore, unlike that of inert chemicals, the quantification of antibodies cannot be standardized using traditional methods. However, there is evidence that the quantification of nucleic acid testing, reporting results in international units, has been successful across many viral load tests. Similarly, traditional methods used to control clinical chemistry testing, such as Westgard rules, are not appropriate for serology testing for infectious diseases, mainly due to variability due to frequent reagent lot changes. This review investigates the reasons why standardization and control of infectious diseases should be further investigated and more appropriate guidelines should be implemented.

Keywords: control; infectious disease; international standards; run control; standardization.

FIG 1

Levey-Jennings chart of quality control results reported over time, with each color indicating results obtained from different reagent lots. Example of lot-to-lot variation in a commonly used anti-HCV-specific immunoassay.