Longitudinal immune cell dynamics and heterogeneous trajectories in children with scrub typhus: a descriptive pilot study

Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi. The dynamic characteristics of immune responses in children with scrub typhus remain unclear. Eight children with confirmed scrub typhus were enrolled in this study. Peripheral blood samples were collected sequentially before and after treatment. Absolute counts of B cell, T cell, dendritic cell, monocyte, and natural killer (NK) cell subsets were measured by multicolor flow cytometry. Linear mixed models and ordinary linear regression analyses were performed to evaluate the dynamics of immune parameters with days after fever onset and days of treatment. A P value < 0.05 was considered statistically significant. Linear mixed models showed that the random intercept variances were zero for all immune subsets. Ordinary linear regression analyses revealed that: absolute counts of total T cells decreased significantly with days of treatment (β = -12066.87, 95% CI: -23966.96 to -166.78, P = 0.04); absolute counts of CD16 + CD14+ double-positive monocytes increased significantly with days of treatment (β = 130.87, 95% CI: 45.24 to 216.50, P = 0.005); absolute counts of CD56dim NK cells increased significantly with days of treatment (β = 1994.06, 95% CI: 337.47 to 3650.65, P = 0.021). Days after fever onset showed no significant effect on CD4/CD8 ratio (β = -0.34, 95% CI: -0.79 to 0.12, P = 0.144), while days of treatment showed a positive trend with CD4/CD8 ratio (β = 0.59, 95% CI: -0.07 to 1.24, P = 0.078). No significant linear associations with days after fever onset or days of treatment were detected for absolute counts of B cell subsets, CD4 + T cells, CD8 + T cells, regulatory T cells, follicular helper T cells, Th1, Th2, Th17, dendritic cells, CD16 + monocytes, total NK cells, CD56bright NK cells, or NKT cells (all P > 0.05). In children with scrub typhus, total T cells decreased with treatment, while CD16 + CD14+ double-positive monocytes and CD56dim NK cells increased with treatment. Most immune subsets showed no significant linear changes associated with disease course or treatment.