An algorithmic approach to identifying the aetiology of acute encephalitis syndrome in India: results of a 4-year enhanced surveillance study.

BACKGROUND: Annual outbreaks of acute encephalitis syndrome pose a major health burden in India. Although Japanese encephalitis virus (JEV) accounts for around 15% of reported cases, the aetiology of most cases remains unknown. We aimed to establish an enhanced surveillance network and to use a standardised diagnostic algorithm to conduct a systematic evaluation of acute encephalitis syndrome in India. METHODS: In this large-scale, systematic surveillance study in India, patients presenting with acute encephalitis syndrome (ie, acute onset of fever with altered mental status, seizure, or both) to any of the 18 participating hospitals across Uttar Pradesh, West Bengal, and Assam were evaluated for JEV (serum and cerebrospinal fluid [CSF] IgM ELISA) per standard of care. In enhanced surveillance, JEV IgM-negative specimens were additionally evaluated for scrub typhus, dengue virus, and West Nile virus by serum IgM ELISA, and for Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, dengue virus, herpes simplex virus, and enterovirus by CSF PCR across five referral laboratories. In 2017, chikungunya and Leptospira serum IgM by ELISA and Zika virus serum and CSF by PCR were also tested. FINDINGS: Of 10 107 patients with acute encephalitis syndrome enrolled in enhanced surveillance between Jan 1, 2014, and Dec 31, 2017, 5734 (57·8%) of 9917 participants with available data were male and 6179 (62·7%) of 9856 were children aged 15 years and younger. Among patients who provided a sample of either CSF or serum in enhanced surveillance, an aetiology was identified in 1921 (33·2%) of 5786 patients enrolled between 2014 and 2016 and in 1484 (34·3%) of 4321 patients enrolled in 2017. The most commonly identified aetiologies were JEV (1023 [17·7%] of 5786 patients), scrub typhus (645 [18·5%] of 3489), and dengue virus (161 [5·2%] of 3124). Among participants who provided both CSF and serum specimens, an aetiology was identified in 1446 (38·3%) of 3774 patients enrolled between 2014 and 2016 and in 936 (40·3%) of 2324 enrolled in 2017, representing a 3·1-times increase in the number of patients with acute encephalitis syndrome with an identified aetiology compared with standard care alone (299 [12·9%]; p<0·0001). INTERPRETATION: Implementation of a systematic diagnostic algorithm in an enhanced surveillance platform resulted in a 3·1-times increase in identification of the aetiology of acute encephalitis syndrome, besides JEV alone, and highlighted the importance of scrub typhus and dengue virus as important infectious aetiologies in India. These findings have prompted revision of the national testing guidelines for this syndrome across India. FUNDING: US Centers for Disease Control and Prevention.

Dengue virus is an under-recognised causative agent of acute encephalitis syndrome (AES): Results from a four year AES surveillance study of Japanese encephalitis in selected states of India.

BACKGROUND: Acute encephalitis syndrome (AES) surveillance in India has indicated that Japanese encephalitis virus (JEV) accounts for 5-35% of AES cases annually; the etiology remains unknown in the remaining cases. We implemented comprehensive AES surveillance to identify other etiological agents of AES, with emphasis on dengue virus. METHODS: Serum and cerebrospinal fluid (CSF) specimens were collected from patients enrolled prospectively in AES surveillance from 2014-2017 at selected sites of three high burden states of India. All samples were initially tested for JEV IgM. Specimens negative for JEV by serology were tested for IgM to scrub typhus, dengue virus (DEN), and West Nile virus; all JEV IgM-negative CSF samples were tested by PCR for S. pneumoniae, N. meningitidis, H. influenzae, herpes simplex virus type 1, enteroviruses and DEN. RESULTS: Of 10,107 AES patients, an etiology could be established in 49.2% of patients including JEV (16%), scrub typhus (16%) and DEN (5.2%) as the top three agents. Amongst the DEN positive cases (359/6892), seven (2%) were positive only for dengue virus RNA: one in serum and six in CSF. CONCLUSION: Amongst the pathogens identified, dengue accounted for 5% of all AES cases and was one of the three common etiological agents. These results underscore the importance of including dengue virus in routine testing of AES cases.

Mycotic corneal ulcers in upper Assam.

PURPOSE: To study the association of various risk factors and epidemiological variables of mycotic keratitis treated at a tertiary referral hospital of upper Assam. MATERIALS AND METHODS: In this hospital-based prospective study a total of 310 consecutive corneal ulcer cases attending the ophthalmology outpatient department of Assam Medical College were enrolled between April 2007 and March 2009. After clinical and slit-lamp biomicroscopic examination in all suspected cases, smears and culture examination for fungus was done to establish the etiology. Demographic information and associated probable risk factors of individual cases were noted in a predesigned questionnaire. RESULTS: In 188 (60.6%) cases fungal etiology could be established. Out of them 67.6% were males. The most commonly affected age group was 41-50 years (25.5%). The maximum (23.4%) cases were reported during the paddy harvesting season in Assam (January and February). Fungal element could be demonstrated in 65.2% cases in direct potassium hydroxide (KOH) mount. The commonest predisposing factor was corneal injury (74.5%). While diabetes was a significant systemic predisposing factor in mixed bacterial and fungal infections in 11.1% cases, blocked naso-lacrimal duct was the local predisposing factor in 11.1% of cases. Fusarium solani (25%) was the commonest isolate followed by Aspergillus species (19%), Curvularia species (18.5%) and Penicillium species (15.2%). Yeasts were isolated in 2.7% (n=5) cases. CONCLUSIONS: Ocular trauma was the commonest cause of fungal corneal ulcer in Assam and Fusarium solani was the commonest species responsible for it. Most of the mycotic ulcer cases come from rural areas including the tea gardens.