Strengthening public health systems for diagnosing patients with acute encephalitis syndrome of unidentified cause
Authors: Nivedita Gupta
Journal: The Lancet Global Health (2022)

The Article by Vasanthapuram Ravi and colleagues1Ravi V Hameed SKS Desai A et al.An algorithmic approach to identifying the aetiology of acute encephalitis syndrome in India: results of a 4-year enhanced surveillance study.Lancet Glob Health. 2022; 10: e685-e693Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar describes the first systematic approach to addressing the complex public health problem of establishing the infectious cause of acute encephalitis syndrome in patients in India, which is still undiagnosed in 45–50% cases across the country. For more than four decades, annual outbreaks of acute encephalitis syndrome have affected children (aged <15 years) across several Indian states. Assam, Bihar, Tamil Nadu, Uttar Pradesh, and West Bengal are the states most affected by the condition, although some cases and deaths are also regularly reported from other states—namely, Tripura, Manipur and Arunachal Pradesh, Karnataka, Odisha, and Jharkhand. Cases of acute encephalitis syndrome in adults are mainly reported from Assam and West Bengal. With the exception of Bihar, where the cause of acute encephalitis syndrome is mainly non-infectious,2Shrivastava A Kumar A Thomas JD et al.Association of acute toxic encephalopathy with litchi consumption in an outbreak in Muzaffarpur, India, 2014: a case-control study.Lancet Glob Health. 2017; 5: e458-e466Summary Full Text Full Text PDF PubMed Scopus (55) Google Scholar other states often report an infectious cause and seasonal distribution of cases.3Murhekar M Vivian Thangaraj JW Mittal M Gupta N Acute encephalitis syndrome in Eastern Uttar Pradesh, India: changing etiological understanding.J Med Entomol. 2018; 55: 523-526Crossref PubMed Google Scholar, 4Khan SA Bora T Laskar B Khan AM Dutta P Scrub typhus leading to acute encephalitis syndrome, Assam, India.Emerg Infect Dis. 2017; 23: 148-150Crossref PubMed Scopus (38) Google Scholar, 5Bandyopadhyay B Bhattacharyya I Adhikary S et al.Incidence of Japanese encephalitis among acute encephalitis syndrome cases in West Bengal, India.Biomed Res Int. 2013; 2013896749Crossref PubMed Scopus (24) Google Scholar, 6Kabilan L Vrati S Ramesh S et al.Japanese encephalitis virus (JEV) is an important cause of encephalitis among children in Cuddalore district, Tamil Nadu, India.J Clin Virol. 2004; 31: 153-159Crossref PubMed Scopus (34) Google Scholar Acute encephalitis syndrome usually occurs in individuals of low socioeconomic status residing in rural areas with poor health-care infrastructure.7Mittal M Bondre V Murhekar M et al.Acute encephalitis syndrome in Gorakhpur, Uttar Pradesh, 2016: clinical and laboratory findings.Pediatr Infect Dis J. 2018; 37: 1101-1106Crossref PubMed Scopus (20) Google Scholar As highlighted by Ravi and colleagues,1Ravi V Hameed SKS Desai A et al.An algorithmic approach to identifying the aetiology of acute encephalitis syndrome in India: results of a 4-year enhanced surveillance study.Lancet Glob Health. 2022; 10: e685-e693Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar Japanese encephalitis virus (JEV) used to be considered the predominant causal agent of acute encephalitis syndrome, which led to the introduction of SA-14–14–2 JEV vaccine in the affected areas through the universal immunisation programme of India. However, despite vaccine introduction, reported cases of acute encephalitis syndrome were not measurably reduced in the affected regions and the cause in about 70–80% of the patients remained undiagnosed.8Srivastava N Deval H Mittal M Kant R Bondre VP The outbreaks of acute encephalitis syndrome in Uttar Pradesh, India (1978–2020) and its effective management: a remarkable public health success story.Front Public Health. 2022; 9793268Crossref PubMed Scopus (2) Google Scholar This situation required focused research to decipher the potential infectious causes of acute encephalitis syndrome, beyond JEV. Through the enhanced surveillance study,1Ravi V Hameed SKS Desai A et al.An algorithmic approach to identifying the aetiology of acute encephalitis syndrome in India: results of a 4-year enhanced surveillance study.Lancet Glob Health. 2022; 10: e685-e693Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar the authors have addressed the important issue of strengthening public health laboratory infrastructure to reduce the proportion of undiagnosed cases. Scrub typhus (Orientia tsutsugamushi) was the most predominant causal agent, accounting for 28·4% of acute encephalitis syndrome cases in Uttar Pradesh, 23·5% in West Bengal, and 6·8% in Assam. Of note, Leptospira was detected in 4·8% of cases in West Bengal and in 4·1% of cases in Assam. Additionally, the authors reported a differential geographical prevalence of dengue virus and chikungunya in acute encephalitis syndrome cases. Both scrub typhus and Leptospira are easily treatable with widely available and affordable drugs, such as doxycycline and azithromycin. If administered early, these antibiotics can cure patients with acute encephalitis syndrome.9Thangaraj JWV Zaman K Shete V et al.Effectiveness of presumptive treatment of acute febrile illness with doxycycline or azithromycin in preventing acute encephalitis syndrome in Gorakhpur, India: a cohort study.Indian Pediatr. 2020; 57: 619-624Crossref PubMed Scopus (4) Google Scholar Of note, after introduction of serum IgM ELISA for scrub typhus and dengue virus at district laboratories, as well as other tests at referral laboratories, there was a 3·1-times increase in the diagnosis of acute encephalitis syndrome cases in 2017, compared with a 2·1-times increase in 2014–16. Ravi and colleagues1Ravi V Hameed SKS Desai A et al.An algorithmic approach to identifying the aetiology of acute encephalitis syndrome in India: results of a 4-year enhanced surveillance study.Lancet Glob Health. 2022; 10: e685-e693Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar describe the establishment of diagnostic ELISA facilities for JEV, dengue virus, and scrub typhus at district hospitals, which are often the first point of contact for local patients with acute encephalitis syndrome. Previous studies have reported that most patients with acute encephalitis syndrome seek health care at a late stage in the disease course, at which point damage can be irreversible, thereby reducing the beneficial effect of drugs and supportive treatment.10Chaturvedi S Sharma N Kakkar M Perceptions, practices and health seeking behaviour constrain JE/AES interventions in high endemic district of North India.BMC Public Health. 2017; 17: 645Crossref PubMed Scopus (5) Google Scholar Early detection and treatment of scrub typhus infection could potentially lead to the complete recovery of a considerable number of patients with acute encephalitis syndrome, who would have otherwise been left undiagnosed and untreated. Detection of dengue virus at peripheral health-care facilities would result in the appropriate management of patients with dengue haemorrhagic fever or dengue shock syndrome. Furthermore, through the overarching referral laboratories, the authors successfully established the serological and molecular diagnosis of dengue NS1 antigen, West Nile virus, chikungunya, Leptospira, Zika virus, Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae, herpes simplex virus type 1, and enteroviruses in acute encephalitis syndrome. Although the contributions of the authors are commendable, sustenance of the valuable public health capacity and expertise that they have created is of crucial importance. Local governments should expand this pilot project, upscale infrastructure in underserved areas, undertake capacity building, ensure adequate funding, organise training for health-care personnel, and provide diagnostic kits and operational equipment. The handling, storage, transport, and referral mechanisms of samples established by the authors should be continued with the same vigour. The core capacities developed in this study should be leveraged to create expertise for deciphering the infectious cause of undiagnosed cases of acute encephalitis syndrome. Capacity for diagnosing cases of leptospirosis, a fully treatable disease, should be established at district hospitals. This action would result in the timely treatment and full recovery of many patients. With the expansion of whole-genome sequencing facilities in India during the COVID-19 pandemic, it would be worthwhile to carry out whole-genome sequencing in a subset of good quality samples collected from patients with acute encephalitis syndrome of undiagnosed cause during the acute phase of illness, to improve our understanding of causes of acute encephalitis syndrome. Key messages from the Article1Ravi V Hameed SKS Desai A et al.An algorithmic approach to identifying the aetiology of acute encephalitis syndrome in India: results of a 4-year enhanced surveillance study.Lancet Glob Health. 2022; 10: e685-e693Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar are that low-income countries, such as India, should focus on strengthening health-care services and laboratory diagnostic capacity at a grass-roots level. This strengthening should also be accompanied with robust referral networks and prompt diagnosis. Early detection of the infectious cause of acute encephalitis syndrome and timely health care can considerably avert morbidity and mortality and can improve the clinical outcomes of patients with various infectious diseases. I declare no competing interests. An algorithmic approach to identifying the aetiology of acute encephalitis syndrome in India: results of a 4-year enhanced surveillance studyImplementation 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. Full-Text PDF Open Access