Natural history of latent brucellosis and diagnostic performance of B-SPOT: a 24-month prospective cohort study based on large-scale screening in northern China

Whether latent brucellosis exists prior to symptom onset and predisposes individuals to active disease remains to be determined. We established a novel ELISpot method for brucellosis (B-SPOT) based on host-specific immune. Diagnostic efficacy was evaluated in a testing cohort comprising brucellosis and non-brucellosis participants. A large-scale screening, using serum agglutination test (SAT) and B-SPOT for latent brucellosis, was later performed in Kangping, a brucellosis-endemic area in northern China, followed by a 24-month prospective cohort study to observe the natural development of latent brucellosis without any intervention. Among 41 brucellosis and 57 non-brucellosis participants, the sensitivity of B-SPOT for brucellosis was 95.1%, and the specificity was 98.2%, compared to the combination of blood culture and SAT. 2459 residents were screened, and the prevalence of latent brucellosis was 3.3% (81/2459). Among 63 latent brucellosis cases successfully followed, 33.3% (21/63) progressed to acute brucellosis within 2 years, while none in the control group progressed(<i>p</i> < 0.001). 16/21 (76.2%) progressed within the first six months, and 14/21 (66.7%) presented with joint pain as their initial symptom. B-SPOT (10.94[95%CI 2.48-48.33, <i>p</i> = 0.002]) outperformed SAT (3.04[95%CI 1.14-8.01, <i>p</i> = 0.026]) in predicting the progression of latent brucellosis. Latent brucellosis accounts for 3.3% in the endemic area, among whom 33.3% progressed to acute brucellosis within two years. The first six months are a critical window, and joint pain is the primary initial symptom. B-SPOT demonstrates high diagnostic efficacy for brucellosis disease activity and can better predict the progression of latent brucellosis.