Association of Scrub Typhus in Children with Acute Encephalitis Syndrome and Meningoencephalitis, Southern India

Abstract

Scrub typhus is an established cause of acute encephalitis syndrome (AES) in northern states of India. We systematically investigated 376 children with AES in southern India, using a stepwise diagnostic strategy for the causative agent of scrub typhus, Orientia tsutsugamushi, including IgM and PCR testing of blood and cerebrospinal fluid (CSF) to grade its association with AES. We diagnosed scrub typhus in 87 (23%) children; of those, association with AES was confirmed in 16 (18%) cases, probable in 55 (63%), and possible in 16 (18%). IgM detection in CSF had a sensitivity of 93% and specificity of 82% compared with PCR. Our findings suggest scrub typhus as an emerging common treatable cause of AES in children in southern India and highlight the importance of routine testing for scrub typhus in diagnostic algorithms. Our results also suggest the potential promise of IgM screening of CSF for diagnosis of AES resulting from scrub typhus.

Keywords: India; Orientia tsutsugamushi; acute febrile encephalopathy; bacteria; central nervous system infections; encephalitis; meningitis/encephalitis; scrub typhus; vector-borne infections.

Figure 1

Laboratory algorithm used for serologic and molecular testing of samples from children with acute encephalitis syndrome, southern India. In case of clinical suspicion of a second-line pathogen, irrespective of the first line test results, second-line tests were performed. Similarly, in the case of clinical suspicion of a third-line pathogen, third-line tests were performed. AES, acute encephalitis syndrome; CSF cerebrospinal fluid.

Figure 2

Results of microbiological tests for scrub typhus (A) and diagnostic association of scrub typhus with acute encephalitis syndrome (B) in children, southern India. AES, acute encephalitis syndrome; CSF, cerebrospinal fluid; OT, Orientia tsutsugamushi.

Figure 3

CSF IgM ELISA results of children with scrub typhus ME, southern India. CSF samples were available in 42/43 children with ME of which CSF IgM was positive in 85.7% children. AES, acute encephalitis syndrome; CSF, cerebrospinal fluid; ME, meningoencephalitis.

Figure 4

District-wise distribution of children with scrub typhus manifesting as acute encephalitis syndrome, southern India. Number of children from each district with scrub typhus manifesting as acute encephalitis syndrome is indicated. The 3 recruiting hospitals and the coordinating center are located in Bangalore urban. Inset shows location of study area in India.