Risk factors for measles among adults in Tianjin, China: Who should be controls in a case-control study?

BACKGROUND Control groups in previous case-control studies of vaccine-preventable diseases have included people immune to disease. This study examines risk factors for measles acquisition among adults 20 to 49 years of age in Tianjin, China, and compares findings using measles IgG antibody-negative controls to all controls, both IgG-negative and IgG-positive. METHODS Measles cases were sampled from a disease registry, and controls were enrolled from community registries in Tianjin, China, 2011-2015. Through a best subsets selection procedure, we compared which variables were selected at different model sizes when using IgG-negative controls or all controls. We entered risk factors for measles in two separate logistic regression models: one with measles IgG-negative controls and the other with all controls. RESULTS The study included 384 measles cases and 1,596 community controls (194 IgG-negative). Visiting a hospital was an important risk factor. For specialty hospitals, the odds ratio (OR) was 4.53 (95% confidence interval (CI): 1.28, 16.03) using IgG-negative controls, and OR = 5.27 (95% CI: 2.73, 10.18) using all controls. Variables, such as age or length of time in Tianjin, were differentially selected depending on the control group. Individuals living in Tianjin ≤3 years had 2.87 (95% CI: 1.46, 5.66) times greater odds of measles case status compared to all controls, but this relationship was not apparent for IgG-negative controls. CONCLUSIONS We recommend that case-control studies examining risk factors for infectious diseases, particularly in the context of transmission dynamics, consider antibody-negative controls as the gold standard.