Predictors of encephalitis in children with scrub typhus-associated acute febrile illness

Scrub typhus (ST) is an emerging public health concern in India. Despite being treatable, 20-30 % of acute febrile illnesses (AFI) progress to encephalitis in endemic regions. This study aimed to identify early markers for encephalitis development in children hospitalized with AFI and positive Orientia tsutsugamushi (Ots) serology. This prospective cohort study was conducted during January-December 2018, involved AFI patients (age ≤ 16 years) tested positive for IgM antibodies against Ots. These patients were followed up prospectively to monitor the development of encephalitis. The clinical and biochemical data from ST-AFI cases developed encephalitis were compared with ST-AFI cases did not develop encephalitis. Univariate and multivariate logistic regression analysis were used to determine predictors of encephalitis. Total 41 out of 190 (21.6 %) ST-AFI patients progressed to encephalitis. The multivariate regression analysis identified initiation of antibiotic therapy after more than 5 days from illness onset (OR 4; 95 % CI [1.4-11.6]), vomiting (>3 episodes) (OR: 10.9; 95 % CI [2.3-51.4]), Glasgow Coma Scale (9-12) (OR 6; 95 %CI [1.9-19]), calcium level (≤8 mg/dL) (OR 6.1 95 % CI [1.1-32.6]), serum creatinine (>1 mg/dL) (OR 16.8, 95 % CI [1.5-191.9]), and oxygen support requirement (OR 19.5, 95 % CI[6.4-59.3]) at admission as predictor of encephalitis in ST-AFI cases. The sensitivity and specificity of model was 67.50 % and 93.96 % respectively, Hosmer-Lemeshow test (χ2 = 8.82, P = 0.3584), and an area under the ROC curve of 0.9514. Study found initiation of antibiotic more than 5 days after illness onset, multiple vomiting episodes, low GCS, hypocalcaemia, high creatinine, and oxygen need as predictors of encephalitis in ST-AFI patients.