Case Report: Survival from Clinical Rabies in a Young Child from Maharashtra, India, 2022.

A 3.5-year-old male child from Maharashtra, India, presented with features of meningoencephalitis approximately 1 month after sustaining severe bite injuries on the right hand from a stray dog. He had received four doses of post-exposure intradermal rabies vaccination (on days 0, 3, and 7 of the bite and erroneously on day 20, instead of day 28 as recommended in the updated Thai Red Cross regimen) as well as local and systemic injections of equine rabies immune globulin. The child was initially diagnosed with and treated for acute encephalitis syndrome before rabies encephalitis was confirmed by detection of rabies virus neutralizing antibodies in the cerebrospinal fluid. During the emergent period, he also received the antimalarial drug artesunate, recently reported to have antiviral effects against rabies virus. With intensive and supportive care, the child showed substantial clinical improvement over the next few weeks. He has now survived for more than 10 months after disease onset, albeit with severe neurological sequelae including diffuse cerebral and cerebellar atrophy.

Thiamine Responsive Acute Infantile Encephalopathy.

This retrospective study was conducted to describe clinical and investigational findings and to determine the effect of thiamine treatment on mortality in patients admitted with acute non-infectious encephalopathy to a hospital in Sikkim between October 2019 and March 2021. Amongst 37 included patients the median age was 4 mo (IQR 3-5), 62.2% were males, 75% were exclusively breastfed infants, 67.6% and 89.2% patients had ophthalmologic and respiratory abnormalities respectively. Multisystem involvement was common. Bilateral basal ganglia involvement was noted in 75% of neuroimaging. Biochemical thiamine deficiency was confirmed in one infant. None of the 11 patients who received thiamine died whereas 20 among 26 patients who did not receive thiamine died [case fatality rate (CFR) 76.9%]. Thiamine treatment was significantly associated with reduced odds of mortality (aOR 0.046, 95% CI 0.0024-0.86, p 0.039). In patients with acute non-infectious encephalopathy and bilateral basal ganglia involvement thiamine use was associated with decreased mortality.

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.

Antiviral effect of Favipiravir against Chandipura virus in vitro and in vivo.

Chandipura virus (CHPV) is an emerging encephalitic virus with outbreak potential in a pediatric population. It causes acute encephalitis, with clinical symptoms leading to death within 48-72 h and an alarmingly high case fatality rate up to 55%-78%. Despite the high mortality rate in children, no vaccines or antivirals are currently available; thus, repurposing licensed drugs seems to be one of the attractive therapeutic approaches. Among the various options available, Favipiravir emerged as a promising candidate, and its unique characteristics and clinical efficacy have garnered significant attention and demonstrated considerable potential in the fight against viral diseases. In the current study, we have evaluated the antiviral effect of Favipiravir against CHPV by Plaque reduction assay and viral growth kinetics assay in Vero cells and in vivo effect of drug treatment against lethal viral challenge was analysed in 10-day-old CD1 mice. A dose-dependent reduction in CHPV plaque size and number was observed in Vero cells treated with Favipiravir, with an EC50 of 92.26 µM. Complete inhibition of CHPV replication was observed at 320 µM drug concentration and 50% cytotoxicity (CC50 ) at 4774 µM, indicating a high selectivity index 51.24. In vivo, studies in mice showed 100% survival with 300 mg/kg/day of Favipiravir given orally till seventh-day postinfection. The study provides evidence of the antiviral activity of Favipiravir against CHPV infection, and further clinical evaluation may alleviate the associated mortality.

Higher replication potential of West Nile virus governs apoptosis induction in human neuroblastoma cells.

The extent of neuronal cell damage caused by West Nile virus (WNV) infection governs the disease severity ranging from mild, febrile illness to fatal encephalitis. Availability of naturally occurring genetic variants is helpful to study viral factors governing differential pathogenesis. During WNV infection, apoptosis serves as a virulence determinant positively contributing to viral pathogenesis. We investigated the levels of apoptosis induced by a low neurovirulent WNV lineage 5 strain 804994 and a high neurovirulent lineage 1 strain 68856 in human neuroblastoma cells, IMR-32. Our investigations clearly show the correlation between higher multiplication capacities of 68856 with higher levels of cytopathology induced by apoptosis. We observed activation of both the extrinsic and intrinsic apoptotic pathways during WNV infection. Infection with higher neurovirulent strain resulted in higher upregulation of pro-apoptotic proteins including death receptors (DR), adaptor protein, BH3-only regulatory proteins and higher cleavage of initiator caspases of both pathways. These results suggest that the virulence of a WNV strain may correlate with its higher replication fitness and ability to cause more cellular damage.

Molecular detection of spotted fever group of Rickettsiae in acute encephalitis syndrome cases from eastern Uttar Pradesh region of India.

The Eastern Uttar Pradesh region of India is known for its endemicity of acute encephalitis syndrome (AES). Decades of research have established that Orientia tsutsugamushi, a causative of scrub typhus, is a substantial contributor (>60%) for the AES cases besides other aetiology, but additional factors in the remaining proportion are still unidentified. Rickettsial infections are challenging to diagnose in clinical settings due to overlapping clinical symptoms, the absence of definitive indicators, a low index of suspicion, and the lack of low-cost, rapid diagnostic tools. Hence, the present study was designed to determine the load of rickettsial infections among AES cases. Furthermore, we aim to find out the prevalent rickettsial species in AES cases as well as in the vector population at this location. The study included the whole blood/cerebrospinal fluid of AES patients and arthropod specimens from rodents. The molecular identification was performed using the 23S-5S intergenic spacer region and ompB gene with genomic DNA obtained from studied specimens. We detected 5.34% (62/1160) of rickettsial infection in AES cases. Among these, phylogenetic analysis confirmed the presence of 54.8% Rickettsia conorii (n = 34) and 16.1% of Rickettsia felis (n = 10), while the rest proportion of the isolates was unidentified at the species level. Furthermore, R. felis was identified in one CSF sample from AES patients and three flea samples from Xenopsylla cheopis. Rickettsia spp. was also confirmed in one Ornithonyssus bacoti mite sample. The results of this investigation concluded the presence of spotted fever group Rickettsia spp. among AES identified cases as well as in the mite and flea vectors that infest rodents.

Extent of disability among paediatric Japanese encephalitis survivors and predictors of poor outcome: a retrospective cohort study in North India.

OBJECTIVE: To determine the Japanese encephalitis (JE)-associated long-term functional and neurological outcomes, the extent of reduced social participation and predictors of poor outcomes among paediatric JE survivors. DESIGN: A retrospective cohort study. SETTING: Laboratory-confirmed JE-positive paediatric cases (<16 years of age) hospitalised at the paediatric ward of Baba Raghav Das Medical College, Gorakhpur, India, between 1 January 2017 and 31 December 2017, were followed up after 6-12 months of hospital discharge. PARTICIPANTS: 126 patients were included in the study; median age was 7.5 years (range: 1.5-15 years), and 74 (58.73%) were male. OUTCOME MEASURES: Functional outcome defined by Liverpool Outcome Score (LOS) dichotomised into poor (LOS=1-2) and good (LOS=3-5) outcome groups compared for demographic, clinical and biochemical parameters for prognostic factors of poor outcomes. Social participation of patients scaled on Child and Adolescent Scale of Participation score 2-5. RESULTS: About 94 of 126 (74.6%) children developed neurological sequelae at different levels of severity. Age-expected social participation was compromised in 90 out of 118 children. In multivariate logistic regression analysis, a combination of parameters, JE unvaccinated status (OR: 61.03, 95% CI (14.10 to 264); p<0.001), low Glasgow Coma Score (GCS) at admission (≤8) (OR: 8.6, 95% CI (1.3 to 57.1); p=0.026), malnutrition (OR: 13.56, 95% CI (2.77 to 66.46); p=0.001) and requirement of endotracheal intubation (OR: 5.43, 95% CI (1.20 to 24.44); p=0.027) statistically significantly predicted the poor outcome with 77.8% sensitivity and 94.6% specificity. The goodness-of-fit test showed that the model fit well (Hosmer-Lemeshow goodness-of-fit test) (χ 2=3.13, p=0.988), and area under the receiver operating characteristic curve was 0.950. CONCLUSION: This study estimates the burden of JE-presenting post-discharge deaths (15.4%) and disability (63.08%). Those who did not receive JE vaccine, were suffering from malnutrition, had GCS ≤8 at admission and required endotracheal intubation had poorer outcomes.

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.

Association of single nucleotide polymorphisms in the CD209, MMP9, TNFA and IFNG genes with susceptibility to Japanese encephalitis in children from North India.

Japanese encephalitis (JE), an acute encephalitis syndrome disease caused by infection with JE virus (JEV), is an important mosquito borne disease in developing countries. The clinical outcomes of JEV infection show inter individual differences. Only in a minor percent of the infected subjects, the disease progresses into acute encephalitis syndrome. Single nucleotide polymorphisms in the host immune response related genes are known to affect susceptibility to JE. In the present study, 238 JE cases and 405 healthy controls (HCs) without any known history of encephalitis were investigated for SNPs in the CD209 MX1, TLR3, MMP9, TNFA and IFNG genes which are important in the immune response against JEV by PCR based methods. The results revealed higher frequencies of heterozygous genotypes of CD209 rs4804803, MMP9 rs17576, TNFA rs1800629 and IFNG rs2430561 in JE cases compared to HCs. These SNPs were associated with JE in an over-dominant genetic model (Odds ratio with 95% CI 1.51 (1.09-2.10) for CD209 rs4804803, 1.52 (1.09-2.11) for MMP9 rs17576, and 1.55 (1.12-2.15) for IFNG rs2430561). The association of G/A genotype of TNFA rs1800629 with JE was confirmed in a larger sample size. The results suggest the association of CD209 rs4804803, MMP9 rs17576, IFNG rs2430561 and TNFA rs1800629 polymorphisms with susceptibility to JE.

Childhood encephalitis hospitalizations associated with virus agents in medium-endemic states in India.

BACKGROUND: Japanese encephalitis (JE) is the leading cause of childhood acute encephalitis syndrome (AES) in India. We enhanced the AES surveillance in sentinel hospitals to determine trends and virus etiologies in central India. METHODS: The neurological hospitalizations among children ≤15 years were tracked by using the AES case definition implemented by the national program. Acute and convalescent sera along with cerebrospinal fluid (CSF) specimens were collected and tested at the strengthened site hospital laboratories for anti-JE, anti-Dengue and anti-Chikungunya virus by IgM ELISA; along with Chandipura virus RT-PCR. Herpes simplex and enterovirus testing was undertaken at the reference laboratory. RESULTS: Among 1619 pediatric neurological hospitalizations reported during 2015-16, AES case definition was fulfilled in 332 (20.5%) cases. After excluding 52 non-AES cases, 280 AES cases resident from study districts were considered eligible for study. The treating physicians diagnosed non-viral causes in 90 cases, therefore 190 (67.9%) of 280 AES cases were suspected with viral etiologies. We enrolled 140 (73.7%) of 190 eligible AES cases. Viral etiologies were confirmed in 31 (22.1%) of 140 enrolled AES cases. JE (n = 22) was the leading cause. Additional non-JE viral agents included Chikungunya (5), Dengue (2) and Chandipura (2). However, only 21 (9.4%) of 222 additional AES cases referred from peripheral hospitals were confirmed as JE. CONCLUSIONS: Japanese encephalitis virus continues to be the leading cause of childhood acute encephalitis syndrome in central India despite vaccination program. Surveillance needs to be intensified for assessing the true disease burden of Japanese encephalitis following vaccination program implementation.

Molecular Detection and Genetic Characterization of Orientia tsutsugamushi from Hospitalized Acute Encephalitis Syndrome Cases During Two Consecutive Outbreaks in Eastern Uttar Pradesh, India.

Background: Seasonal outbreaks of acute encephalitis syndrome (AES) have been reported especially in the pediatric population with a high case fatality rate in Eastern Uttar Pradesh, India. Orientia tsutsugamushi (OT) is a causative agent of scrub typhus that has been recently identified as a major cause of AES. However, the specific genotypes of OT responsible for AES cases of this region are not known. Therefore, the present study was undertaken to understand the molecular epidemiology of OT prevailing in the AES endemic Eastern Uttar Pradesh region of India. Methods: The study was conducted on 2529 hospitalized AES cases from August 2016 to December 2017. The presence of antibodies against OT from cerebrospinal fluid (CSF) and serum samples were tested using OT IgM enzyme-linked immunosorbent assay (ELISA), whereas OT DNA was tested from whole blood and CSF specimens targeting the partial gene of 56 kDa using nested PCR. Phylogenetic analysis was conducted with sequences (n = 241) generated in this study. Findings: Among the studied AES cases, 50% were found positive for antibodies against OT, whereas 37% of cases were positive for OT DNA. The genetic analysis study revealed that Gilliam (93.8%) is the prevailing genotype of OT followed by Karp (6.16%) genotype in AES cases. Furthermore, the Gilliam strains of this study showed they were >99% identical to earlier reported Gilliam strains from AES cases. Conclusion: We observed the presence of two main OT genotypes in AES cases, among which the majority of OT genotypes fall under the Gilliam clade. The understanding of predominant genotype will be beneficial for its future implications in vaccine development strategies and the development of rapid diagnostic tests.

Abundance of Ticks (Acari: Ixodidae) and Presence of Rickettsia and Anaplasma in Ticks Infesting Domestic Animals From Northern India.

Rickettsia and Anaplasma are bacteria that can be transmitted by hematophagous arthropods such as ticks infesting animals in close proximity to humans. The main objective of the present study was to investigate abundance of common tick species infesting domestic animals and presence of Rickettsia and Anaplasma in tick populations. Adult ticks were collected from domestic animals in rural areas and screened by molecular detection of bacterial DNA for these two genera of bacteria. A total of 1,778 adult ixodid tick specimens were collected from 200 cattle, 200 buffaloes, 200 goats, and 40 dogs. The collection consisted of four species of ixodid ticks, Rhipicephalus (Boophilus) microplus (Canestrini) (83.8%), Hyalomma kumari (Sharif) (7.1%), Rhipicephalus sanguineus (Latreille) (6.4%), and Dermacentor auratus (Supino) (2.7%) infesting the domestic animals. The prevalence of all the collected tick species was highest in the month of October. Anaplasma spp. was the most frequently identified bacteria (3.3%) in tested ticks. Of 17 positive tick pools for Anaplasma spp., 14 pools were from ticks infesting cattle, 2 pools of ticks collected from buffalo, and the remaining pool were ticks infesting a goat at the time of collection. Although 1.6% tick pools of R. microplus collected from cattle tested positive for Rickettsia spp., present investigation provides evidence of the most prevalent ixodid ticks infesting domestic animals and the presence of obligate intracellular bacteria, Rickettsia and Anaplasma, in these ticks collected in the Gorakhpur division of Northern India.

The Outbreaks of Acute Encephalitis Syndrome in Uttar Pradesh, India (1978-2020) and Its Effective Management: A Remarkable Public Health Success Story.

INTRODUCTION: Acute encephalitis syndrome (AES) is a major public health enigma in India and the world. Uttar Pradesh (UP) is witnessing recurrent and extensive seasonal AES outbreaks since 1978. Government of India and UP state government have devised various mitigation measures to reduce AES burden and AES associated mortality, morbidity and disability in Uttar Pradesh. The aim of this study was to describe the public health measures taken in order to control seasonal outbreaks of AES in UP between 1978 and 2020. METHODS: We used literature review as a method of analysis, including the Indian government policy documents. This review utilized search engines such as PubMed, Google Scholar, Research Gate, Cochrane, Medline to retrieve articles and information using strategic keywords related to Acute Encephalitis Syndrome. Data was also collected from progress reports of government schemes and websites of Indian Council of Medical Research (ICMR), National Vector Borne Disease Control Programme (NVBDCP) and Integrated Disease Surveillance Programmes (IDSP). RESULTS: The incidence of AES cases in UP have declined from 18.2 per million population during 2005-2009 to 15 per million population during 2015-2019 [CI 12.6-20.6, P-value < 0.001] and case fatality rate (CFR) reduced from 33% during 1980-1984 to 12.6% during 2015-2019 [CI 17.4-30.98, P-value < 0.001]. AES incidence was 9 (2019) and 7 (2020) cases per million populations respectively and CFR was 5.8% (2019) and 5% (2020). This decline was likely due to active surveillance programs identifying aetiological agents and risk factors of AES cases. The identified etiologies of AES include Japanese encephalitis virus (5-20%), Enterovirus (0.1-33%), Orientia tsutsugamushi (45-60%) and other viral (0.2-4.2%), bacterial (0-5%) and Rickettsial (0.5-2%) causes. The aggressive immunization programs against Japanese encephalitis with vaccination coverage of 72.3% in UP helped in declining of JE cases in the region. The presumptive treatment of febrile cases with empirical Doxycycline and Azithromycin (EDA) caused decline in Scrub Typhus-AES cases. Decrease in incidence of vector borne diseases (Malaria, Dengue, Japanese Encephalitis and Kala Azar) i.e., 39.6/100,000 population in 2010 to 18/100,000 population in 2017 is highlighting the impact of vector control interventions. Strengthening healthcare infrastructure in BRD medical college and establishment of Encephalitis Treatment Centre (ETC) at peripheral health centres and emergency ambulance services (Dial 108) reduced the referral time and helped in early treatment and management of AES cases. The AES admissions increased at ETC centres to 60% and overall case fatality rate of AES declined to 3%. Under clean India mission and Jal Jeevan mission, proportion of population with clean drinking water increased from 74.3% in 1992 to 98.7% in 2020. The proportion of household having toilet facilities increased from 22.9% in 1992 to 67.4% in 2020. Provisions for better nutritional status under state and national nutrition mission helped in reducing the burden of stunting (52%) and wasting (53.4%) among under five children in 1992 to 38.8% (stunting) and 36.8% (wasting) in year 2018. These factors have all likely contributed to steady AES decline observed in UP. CONCLUSION: There is a recent steady decline in AES incidence and CFR since implementation of intensive AES surveillance system and JE immunization campaigns which is highlighting the success of interventions made by central and state government to control seasonal AES outbreaks in UP. Currently, AES incidence is 9 cases per million population (in year 2019) and mortality is 5.8%.

Genetic characterization of dengue virus serotype 2 isolated from dengue fever outbreaks in eastern Uttar Pradesh and western Bihar, India.

Dengue (DEN) is the most common cause of mosquito-borne endemic viral diseases in the tropical and subtropical countries. DEN outbreaks associated with multiple dengue virus (DV) serotypes have been regularly reported in different parts of India. This study was done during DEN outbreaks in 2015 to 2016 in UP and Bihar where DEN-2 was found as the only prevalent serotype. DV-2 was the only serotype amplified in serotype-specific reverse-transcription polymerase chain reaction from sera of 210 (65.21%) out of 322 DV NS1 antigen-positive patients. Further genetic analysis based on full-length envelope (E) protein sequence derived from patient's sera as well as DV isolate showed the circulation of lineages I and III of DV-2 cosmopolitan genotype during 2015 and lineage II during 2016. Finally, the phylogenetic analysis using the E gene sequence revealed that these DV-2 strains have a close genetic relationship with the recently reported DV-2 genotypes from DEN outbreaks reported from different parts of north India. These results showed the circulation of cosmopolitan genotype of DV-2 in eastern Uttar Pradesh and western Bihar, India. The genetic database generated on circulating DV strains in this study will be useful as reference for disease surveillance and strengthening laboratory diagnosis protocols.

Detection of Immunoglobulin M and Immunoglobulin G Antibodies Against Orientia tsutsugamushi for Scrub Typhus Diagnosis and Serosurvey in Endemic Regions.

OBJECTIVE: To estimate the regional cutoff of optical density (OD) values for immuno-globulin M (IgM) antibodies against Orientia tsutsugamushi in serum and cerebrospinal fluid (CSF) for clinical diagnosis of scrub typhus and immunoglobulin G (IgG) antibodies in serum for sero-epidemiology in Gorakhpur, Uttar Pradesh, India. METHODS: We used data from a serological investigation of acute encephalitis syndrome patients (n=407) during the 2016 outbreak in Gorakhpur, India to determine the cutoff for OD values for IgM antibodies, and from community-based serosurveys (n=1991) to estimate the cutoff for OD values for IgG antibodies. RESULTS: We determined regionally relevant cutoff for OD values of 0.76 for IgM antibodies in serum and 0.22 in cerebrospinal fluid for scrub typhus diagnosis. For serosurveys, IgG antibody cutoff was 1.5. CONCLUSION: We have proposed locally relevant cutoffs for scrub typhus endemic regions, which may be useful for correctly classifying infected population.

Association of single nucleotide polymorphisms in TNFA and CCR5 genes with Japanese Encephalitis: A study from an endemic region of North India.

TNFA, IL1B, HMGB1, IL10, CXCL8, CCL2 and CCR5 gene polymorphisms were investigated in 183 Japanese Encephalitis (JE) cases and 361 healthy controls from North India. Higher frequency of TNFA rs1800629 G/A, CCR5 rs1799987 genotypes with A allele and lower frequency of combination lacking TNFA rs1800629 A, CCR5 rs333 Δ32, andCCR5 rs1799987 A alleles and CCL2 rs1024611 G/G genotype was observed in JE cases. TNFA rs1800629 A and CCR5 rs1799987 A alleles were associated with susceptibility while combination lacking TNFA rs1800629 A, CCR5 rs333 Δ32, and rs1799987 A alleles and CCL2 rs1024611 G/G genotype was associated with protection to JE.

Acute Encephalitis Syndrome in Gorakhpur, Uttar Pradesh, 2016: Clinical and Laboratory Findings.

BACKGROUND: Seasonal outbreaks of acute encephalitis syndrome (AES) with high fatality have been occurring in Gorakhpur, Uttar Pradesh, India, for several years. We conducted investigations during the 2016 outbreak to identify the etiology. METHODS: We included 407 hospitalized AES patients with cerebrospinal fluid pleocytosis (>5 cells/mm) in our study. These patients were clinically examined; their blood and cerebrospinal fluid samples were collected and investigated for scrub typhus (ST), Japanese encephalitis virus (JEV), dengue virus and spotted fever group of Rickettsia by serology and/or polymerase chain reaction. RESULTS: Of the 407 AES patients, 266 (65.4%), 42 (10.3%) and 29 (7.1%) were diagnosed to have ST, JEV and dengue infection, respectively. Four patients were diagnosed to have spotted fever group of Rickettsia infection. A significantly higher proportion of ST patients with AES had hepatomegaly, splenomegaly and facial edema. The common hematologic and biochemical abnormalities among ST-positive patients include thrombocytopenia, raised liver enzymes and bilirubin levels. The case fatality ratio was significantly higher among ST-negative AES patients (36.2% vs. 15.2%; P < 0.05). CONCLUSIONS: ST accounted for approximately two third of the AES case-patients. Efforts are required to identify the etiology of AES case-patients who are negative for ST, JEV and dengue fever.