Scrub typhus is now the most common infectious cause of acute encephalitis syndrome in southern India

A large multicentre study of 587 children with acute encephalitis syndrome (AES) from Karnataka, Andhra Pradesh, and Tamil Nadu has revealed that scrub typhus, a bacterial infection, is now the most common infectious cause of AES in southern India.

The study by a team of researchers from NIMHANS, Indira Gandhi Institute of Child Health, Bangalore Medical College and Research Institute, and St. John’s Medical College Hospital has been recently published in The Lancet Regional Health - Southeast Asia.

Global challenge

AES, characterised by acute onset fever and altered mental status and/or new seizures, presents a significant global public health challenge. It has an incidence of 3.5 to 13.8 cases per 1,00,000 patient-years, disproportionately affects children, and is associated with high morbidity and mortality.

In India, over 10,000 cases of AES are reported annually to the National Vector Borne Disease Control Programme (NVBDCP).

Historically, surveillance efforts have prioritised Japanese encephalitis (JE), even as its incidence has significantly declined due to widespread vaccination. Moreover, recent studies reveal a dynamic, region-specific, and evolving aetiology of AES in India. Scrub typhus (caused by bacterium Orientia tsutsugamushi), an under-recognised cause of AES, has been increasingly reported in certain regions.

Aimed at systematically investigating infectious aetiologies of AES in children from southern India and developing clinical prediction models for diagnosing scrub typhus, the study found that the bacterial infection is now the most common infectious cause (44%) of AES in southern India, far exceeding Japanese encephalitis virus (11%).

Scrub typhus and other doxycycline-treatable infections are significant contributors of AES in India. However, limited surveillance in southern India has hindered their recognition and the inclusion of doxycycline in treatment protocols. 

From tertiary care hospitals

The prospective study enrolled children aged above 28 days to 18 years with AES presenting to three tertiary care hospitals in Bengaluru - Indira Gandhi Institute of Child Health, Vani Vilas, and St. John Medical College Hospital. Primary outcomes were microbiological diagnosis of AES and clinical prediction models for diagnosing scrub typhus and identifying patients with doxycycline-treatable causes. Models were developed using multivariable logistic regression, internally validated, and simplified into point-scoring systems. 

Between March 2020 and February 2023, 714 children were screened, of whom 587 were included. Of these, 315 (54%) had a microbiological diagnosis. Scrub typhus accounted for 138/315 (44%), and doxycycline-treatable causes were diagnosed in 193/315 (61%) of these cases. Key predictors associated with both scrub typhus and doxycycline-treatable causes were age, illness duration, lymphadenopathy, oedema, hepatomegaly, lymphocyte count, platelet count, and serum albumin levels, said Tina Damodar, clinical virologist and DBT-Welcome Trust fellow, Department of Neurovirology at NIMHANS, who is the lead author of the study.

“Among the 315 children with an identified infectious cause, dengue (10%), leptospira (5%), and chikungunya (5%) were also notable. Other detected pathogens included herpes viruses, enteroviruses, pneumococcus, tuberculosis, and measles, reflecting a diverse and region-specific AES landscape. These findings highlight the need to update AES surveillance and treatment protocols,” Dr. Damodar told The Hindu on Thursday.

“The study found that over 60% of microbiologically confirmed AES cases were caused by doxycycline-treatable infections, primarily scrub typhus. Despite this, doxycycline is not routinely included in empirical AES treatment in many parts of India,” she said.

Recommendation

Another author Reeta S. Mani, head of Neurovirology at NIMHANS, said that based on the results, the study recommends including doxycycline or azithromycin in the initial treatment of children with AES or acute febrile illness (AFI) in southern India - a change already implemented at the participating referral tertiary care hospitals.

“Timely treatment is critical. Among the 138 children with scrub typhus, nearly 40% either died or developed neurological complications, largely due to delayed diagnosis. To address this, the study calls for wider availability of scrub typhus diagnostic tests (IgM ELISA or PCR) at primary and secondary care levels,” the doctor said.

The researchers have also developed a clinical prediction model - a simple point-based tool that can help frontline clinicians identify children likely to benefit from doxycycline, even before lab confirmation is available.