Incidence of Japanese Encephalitis and Acute Encephalitis Syndrome Hospitalizations in the Medium-Endemic Region in Central India.

BACKGROUND: We estimated the incidence of Japanese encephalitis (JE) and acute encephalitis syndrome (AES) following routine immunization with the live-attenuated SA 14-14-2 JE vaccine. METHODS: We implemented enhanced surveillance of AES and JE hospitalizations in endemic districts in Maharashtra and Telangana States during 2015-2016 and 2018-2020. We estimated incidence and compared differences in the incidence of JE and AES between two states, and vaccinated and unvaccinated districts during two study periods. We also considered secondary data from public health services to understand long-term trends from 2007 to 2020. RESULTS: The annual AES incidence rate of 2.25 cases per 100,000 children in Maharashtra during 2018-2020 was significantly lower than 3.36 cases per 100,000 children during 2015-2016. The six JE-vaccinated districts in Maharashtra had significantly lower incidence rates during 2018-2020 (2.03, 95% CI 1.73-2.37) than in 2015-16 (3.26, 2.86-3.70). In addition, the incidence of both JE and AES in two unvaccinated districts was higher than in the vaccinated districts in Maharashtra. Telangana had a lower incidence of both JE and AES than Maharashtra. The AES incidence rate of 0.95 (0.77-1.17) during 2018-2020 in Telangana was significantly lower than 1.67 (1.41-1.97) during 2015-2016. CONCLUSIONS: The annual incidence rate of Japanese encephalitis was < 1 case per 100,000 children. It indicated accelerated control of Japanese encephalitis after routine immunization. However, the annual incidence of acute encephalitis syndrome was still > 1 case per 100,000 children. It highlights the need for improving surveillance and evaluating the impacts of vaccination.

Infectious causes of acute encephalitis syndrome hospitalizations in Central India, 2018-20.

BACKGROUND: We enhanced surveillance of hospitalizations of all ages for acute encephalitis syndrome (AES) along with infectious aetiologies, including the Japanese encephalitis virus (JEV). METHODS: From October 2018 to September 2020, we screened neurological patients for AES in all age groups in Maharashtra and Telangana States. AES cases were enrolled at study hospitals along with other referrals and sampled with cerebrospinal fluid, acute and convalescent sera. We tested specimens for non-viral aetiologies viz. leptospirosis, typhoid, scrub typhus, malaria and acute bacterial meningitis, along with viruses - JEV, Dengue virus (DENV), Chikungunya virus (CHIKV), Chandipura virus (CHPV) and Herpes simplex virus (HSV). RESULTS: Among 4977 neurological hospitalizations at three study site hospitals over two years period, 857 (17.2%) were AES. However, only 287 (33.5%) AES cases were eligible. Among 278 (96.9%) enrolled AES cases, infectious aetiologies were identified in 115 (41.4%) cases, including non-viral in 17 (6.1%) cases - leptospirosis (8), scrub-typhus (3) and typhoid (6); and viral in 98 (35.3%) cases - JEV (58, 20.9%), HSV (22, 7.9%), DENV (15, 5.4%) and CHPV (3, 1.1%). JEV confirmation was significantly higher in enrolled cases than referred cases (10.2%) (p < 0.05). However, the contribution of JEV in AES cases was similar in both children and adults. JE was reported year-round and from adjacent non-endemic districts. CONCLUSIONS: The Japanese encephalitis virus continues to be the leading cause of acute encephalitis syndrome in central India despite vaccination among children. Surveillance needs to be strengthened along with advanced diagnostic testing for assessing the impact of vaccination.

Delineation of an epitope recognized by a chikungunya virus anti-capsid monoclonal antibody on the protease domain using an immuno-informatics approach.

The capsid-protein (CP) of chikungunya virus (CHIKV) is reported to generate a primary immune response in infected individuals during disease progression. CP-specific monoclonal antibodies (mAbs) developed in our laboratory, exhibited promising potential in diagnosing recent CHIKV infection in IgM capture ELISA. In this study we focused on the molecular and structural characterization of one such representative mAb ClVE4/D9 to delineate the epitope recognized by it using an immuno-informatics approach. The antigen-antibody interacting residues were found to lie within the dimer interface region of the CP, also predicted as a conformational epitope. This implies that the mAb could interfere during the process of nucleocapsid assembly, ultimately preventing budding and egress of the virus particle. The binding specificity of the mAb highlights the possibility of using this anti-CP antibody for therapeutic or prophylactic treatment against CHIKV.Communicated by Ramaswamy H. Sarma.

Acute Encephalitis with Atypical Presentation of Rubella in Family Cluster, India.

We report 3 atypical rubella cases in a family cluster in India. The index case-patient showed only mild febrile illness, whereas the other 2 patients showed acute encephalitis and died of the disease. We confirmed rubella in the index and third cases using next-generation sequencing and IgM.

Identification of a conserved neutralizing epitope in the G-protein of Chandipura virus.

Chandipura virus (CHPV), associated with an encephalitic illness in humans, has caused multiple outbreaks with high mortality in central and western India in recent years. The present study compares surface glycoprotein (G-protein) from prototype and recent outbreak strains using in silico tools and in vitro experiments. In silico epitope predictions (B-cell and T-helper cell) for the sequences, 3D structure prediction and comparison of the G-proteins of the strains: I653514 (Year 1965), CIN0327 (Year 2003) and 148974 (Year 2014) revealed that the CHPV G-protein is stable and antigenic determinants are conserved. A monoclonal antibody developed against strain CIN0327 (named NAbC) was found to neutralize prototype I653514 as well as the currently circulating strain 148974. In silico antigen-antibody interaction studies using molecular docking of predicted structures of NAbC and G-proteins of various CHPV strains led to the identification of a conserved neutralizing epitope in the fusion domain of G-protein, which also contained a putative T-helper peptide. The identification of a conserved neutralizing epitope in domain IV (fusion domain amino acids 53 to 172) of CHPV G-protein is an important finding that may have the scope towards the development of protective targets against CHPV infection.

Molecular Evidence of Chandipura Virus from Sergentomyia species of Sandflies in Gujarat, India.

The spread and establishment of Chandipura virus (CHPV) infection in India has raised serious epidemiological concerns. The virus interface with the vertebrate hosts (including humans) and vector competence are the important parameters of disease prevalence. Interestingly, in the present study, a highly zoophilic species of the sandfly Sergentomyia was found to be a potential vector of CHPV in Gujarat. This is probably the first report from India of male sandflies testing positive for CHPV in RT-PCR analysis. These findings signify vertical transmission of the virus among sandflies and have epidemiological significance. Health Officers from Gujarat referred 9 pools comprising 277 adult sandflies from disease-affected and unaffected areas to the National Institute of Virology, Pune. The pools were subjected to RT-PCR analysis and sequencing. Of the 9, 2 female and one male pool tested positive for CHPV. Phylogenetic analysis showed similarity of the new sandfly-borne CHPV strains with the human strain from Andhra Pradesh (AP) 2003. The present study highlights the possible role of Sergentomyia spp. in the transmission of CHPV in India.

A large outbreak of Japanese encephalitis predominantly among adults in northern region of West Bengal, India.

Unusual rise of acute encephalitis syndrome cases (AES) were reported in July 2014 in the northern region of West Bengal, India. Investigations were carried out to characterize the outbreak and to identify the associated virus etiology. This observational study is based on 398 line listed AES cases, mostly (70.8%, 282/398) adults, with case fatality ratio of 28.9% (115/398). Japanese encephalitis virus infection was detected in 134 (49.4%) among 271 AES cases tested and most of them (79.1%, 106/134) were adults. The study reports a large outbreak of genotype III Japanese encephalitis among adults in northern region of West Bengal, India. J. Med. Virol. 88:2004-2011, 2016. © 2016 Wiley Periodicals, Inc.

Respiratory viruses in acute respiratory tract infections in Western India.

OBJECTIVE: To study the circulation pattern of respiratory viruses in out patients department (OPD) and hospitalized children with acute respiratory tract infection. METHODS: Nasopharyngeal aspirates were collected from 385 children with acute respiratory tract infections attending the OPD (n=199, 51.7%) and admitted to pediatric ward (n=186, 43.2%). Specimens were screened for seven respiratory viruses by immunofluoresence test (IFT) using Respiratory panel 1 screening and identification kit. RESULTS: Viral antigens were detected in 57 (28.6%) and 86 (46.2%) patients from OPD and admitted cases respectively, giving an overall positivity of 143 (37.1%) for respiratory viruses. Of the six respiratory viruses, the most common was respiratory syncytial virus (RSV) in 100 (26%) patients, followed by influenza viruses in 21 (5.4%), parainfluenza in 8 (2.07%), adenovirus in 3 (0.8%). One patient had mixed infection of RSV and adenovirus. RSV was most frequently detected in the hospitalized children (39.8%). CONCLUSION: RSV appeared to be the most common respiratory viral infection in the age group 0-1 year causing hospitalization.