Risk factors for development of paradoxical response during antituberculosis therapy in HIV-negative patients

The risk factors for development of paradoxical response were studied in a cohort of 104 patients with culture-documented Mycobacterium tuberculosis infection. Paradoxical deterioration occurred in 16 (15.4%) patients (case group) during antituberculosis therapy, involving lungs and pleura (n=4), spine and paraspinal tissue (n=5), intracranium (n=3), peritoneum (n=2), bone and joint (n=1), and lymph node (n=1). The median time from commencement of treatment to paradoxical deterioration was 56 days (range, 20-109 days). Compared with 53 patients without clinical deterioration after antituberculosis therapy (control group), patients with paradoxical response were more likely to have extrapulmonary involvement (62.5% vs. 17.0%; P<0.05) at initial diagnosis, to have lower baseline lymphocyte counts (672+/-315 cells/microl vs. 1,328+/-467 cells/microl; P<0.001), and to exhibit a greater surge in lymphocyte counts (627+/-465 cells/microl vs. 225+/-216 cells/microl; P<0.05) during paradoxical response. Further studies on lymphocyte subsets and cytokine levels would be useful in understanding the exact immunological mechanisms involved in immunorestitution.