Prediction Rule for Scrub Typhus Meningoencephalitis in Children: Emerging Disease in North India

Abstract

Objectives: To evaluate the proportion of scrub typhus meningoencephalitis among children with acute encephalitis syndrome and to outline its differentiating features. To develop a prediction rule for scrub typhus meningoencephalitis. Methods: A prospective cohort study was conducted at a tertiary care public hospital in Northern India. Consecutive patients of acute encephalitis syndrome who met our inclusion criteria were enrolled over 2 years. Standardized workup including serum IgM against Orientia tsutsugamushi was performed. Clinical and laboratory features were compared between IgM-positive and IgM-negative patients. The area under the receiver operating characteristic curve of the score derived from “independent predictors” was measured. Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were calculated at different cut-offs of the score. Results: Scrub typhus IgM enzyme-linked immunosorbent assay was positive in 66/352 patients (18.8%). Longer duration of fever and prodromal stage along with eschar, hepatomegaly, lymphadenopathy, and pneumonia were significantly more prevalent in scrub typhus meningoencephalitis. However, petechiae were frequent in non–scrub typhus patients. Leucocytosis, lymphocytosis, thrombocytopenia, hypoalbuminemia, and elevated levels of serum bilirubin, serum transaminases, and cerebrospinal fluid protein were associated with scrub typhus meningoencephalitis. Logistic regression revealed fever for >8 days, pneumonia, absence of petechiae, cerebrospinal fluid protein >1000 mg/L, and serum glutamic oxaloacetic transaminase >100 IU/L as independent “predictors” of scrub typhus meningoencephalitis. The area under the receiver operating characteristic curve (95% confidence interval) of the prediction score was 0.832 (0.78-0.89). Score at cutoff ≥1 had 91% sensitivity, 96.1% negative predictive value, and at cutoff ≥4 had 99.7% specificity, 88.9% positive predictive value, 83.1% negative predictive value, 40.3 positive likelihood ratio, 0.88 negative likelihood ratio for identifying scrub typhus meningoencephalitis. Conclusion: Prediction score may help physicians in peripheral areas to identify and treat scrub typhus meningoencephalitis, an emerging cause of acute encephalitis syndrome in India.

Neurological manifestations of scrub typhus infection: A systematic review and meta-analysis of clinical features and case fatality

“…Furthermore, all studies included in our meta-analyses recruited from either tertiary or teaching hospitals and the clinicians at sites recruiting patients may be more adept at recognising and managing neurological scrub typhus infections. This reduces the generalisability of our results and fatality may be higher in settings where fewer specialists are available; more studies are needed in other settings in the tsusugamushi triangle , particularly from rural regions where burden of scrub typhus is high [ 12 , 62 ].…”

“…The mean (SD) age was 29.1 (19.0) and 573 (46.9%) were female. Patients presented to hospital after a median (IQR) duration of symptoms of 7.9 (7.0-9.2) days and had a median (IQR) Glasgow coma scale (GCS) score of 11/15 (9)(10)(11)(12)(13)(14)(15). Complete treatment data were available for 859 cases of whom 389 (45.3%) were treated with doxycycline monotherapy and 379 (44.1%) with azithromycin only.…”

“…Prompt antibiotic therapy relies on early recognition of scrub typhus. Though small, single-site studies from a select few geographical regions have reported the clinical features CNS scrub typhus [8,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29], these have not been systematically analysed to help understand when clinicians should consider a diagnosis of scrub typhus CNS disease.…”

Encephalitis and Brain Abscess

“…Systemic involvement in the setting of scrub typhus is common, most frequently lymphadenopathy, hepatomegaly, and laboratory evidence of transaminitis and thrombocytopenia. 57 EUKARYOTIC PARASITES. Helminths and amoebas are important causes of encephalitis in the United States and worldwide.…”

“…Notably, rickettsial species are distributed globally and Orientia tsutsugamushi , the causative agent of scrub typhus, is increasingly recognized as a cause of encephalitis in South Asia. Systemic involvement in the setting of scrub typhus is common, most frequently lymphadenopathy, hepatomegaly, and laboratory evidence of transaminitis and thrombocytopenia 57 …”