Antinuclear antibodies in scrub typhus: Transient occurrence during acute illness

Background & objectives: The pathological hallmark of scrub typhus infection is focal or disseminated vasculitis. As with other infections, antinuclear antibodies (ANA) have been previously described in scrub typhus. However, the underlying mechanisms and implications of this immunological phenomenon is not well understood. In the present work it was assessed whether ANA is associated with illness severity and outcomes. Methods: In this prospective study spanning one year, patients fulfilling the diagnostic criteria for scrub typhus were recruited. Patients with other acute infective febrile illnesses were taken as controls. ANA positivity was compared between the cases and controls. ANA in scrub typhus was assessed for correlation with disease severity, organ dysfunction and outcomes. Results: The cohort comprised of 149 patients (scrub 89; controls 60) with mean age 46.5 (SD=16.9) yr, 48.3% were female. ANA was detected in 48 (53.9%) patients with scrub typhus and 9(15%) controls (p < 0.001). The ANA pattern was predominantly speckled (93.8%) in both scrub typhus patients and controls. In patients with scrub typhus, ANA positivity was associated with increasing APACHE-III score [Odds ratio (OR) 1.01; 95% CI 0.99-1.03; p = 0.09]. On bivariate analysis, ANA tended to be correlated with acute respiratory distress syndrome (OR 2.32; 95% CI 0.98-5.46; p = 0.06), hepatic dysfunction (OR 2.25; 95% CI 0.94-5.39, p = 0.06) and aseptic meningitis (OR 6.83; 95% CI 0.80-58.05,p = 0.08). The presence of these antibodies did not correlate with duration of hospitalization or mortality. Convalescent sera on 31 ANA positive scrub typhus patients demonstrated persistence of ANA in only 5 (16.1%) patients. Interpretation & conclusion: The disappearance of ANA during the convalescent phase suggests that ANA is expressed during the acute phase of scrub typhus infection. Its association with organ dysfunction warrants further study of the mechanisms and impact of autoantibody formation in scrub typhus.