Immunogenicity & safety of a single dose of live-attenuated Japanese encephalitis vaccine SA 14-14-2 in adults.

BACKGROUND & OBJECTIVES: Japanese encephalitis (JE) caused by mosquito-borne Flavivirus is one of the leading causes of viral encephalitis in Asia. Control strategies include vector control and human vaccination. Due to lack of immunization programmes in endemic regions, there are still high mortality and morbidity. A live-attenuated SA 14-14-2 JE vaccine (LAJEV) has been licensed and used in Asian countries, including India. We report the assessment of immunogenicity and safety of the vaccine in adults during the first mass adult vaccination campaign carried out in Assam, India. METHODS: One thousand and seventy five adults (aged ≥15 yr) who received LAJEV were monitored for adverse events following immunization for one year. The safety assessment of vaccinated population was evaluated till 28 days and at 6 and 12 months. Blood samples collected from the enrolled participants were tested by plaque reduction neutralization test (PRNT 50 ) to assess the neutralizing antibody titres (NATs) before vaccination and 28 days, six and 12 months post-vaccination (PV). RESULTS: Among the 1075 vaccinated individuals, four reported minor adverse effects from 30 min to 28 days PV. Based on the pre-vaccination NAT, the study participants were categorized as seronegative, moderately seropositive and strongly seropositive. Nearly 85.5 per cent of JE seronegative participants seroconverted by 28 days PV. The geometric mean titre (GMT) in all the three groups increased by 28 days and decreased by six and 12 months PV. Nearly 60 per cent of the moderately positive individuals exhibited four-fold rise in GMT, 28 days PV. Almost 95.5 per cent of the participants in the study population remained seroprotected at the end of 12 months PV. INTERPRETATION & CONCLUSIONS: This study on immunogenicity and safety of LAJEV in adults showed that a single dose of the live-attenuated vaccine was safe and induced protective immunity to both JE seronegative and naturally seropositive adults. Further study is required to find out long term protective efficacy of this vaccine.

Chikungunya outbreak in Garo Hills, Meghalaya: An epidemiological perspective.

BACKGROUND & OBJECTIVES: Chikungunya (CHIK) fever is a mosquito-borne disease caused by chikungunya virus (CHIKV). Chikungunya infection was first reported from India in 1963 from Kolkata. We report the serological and molecular evidence of an outbreak of chikungunya in northeast India that occurred in Tura, a hilly and forested terrain in Garo Hills district of Meghalaya. METHODS: Blood samples (3 ml) collected from hospitalized patients during the outbreak were tested for IgM antibodies against CHIKV and followed up four months later. A repeat survey was carried out in the same area after four months from where cases had been reported. Blood samples were also collected from people with history of fever and body ache in the last four months. Persons showing IgM positivity against CHIKV in the repeat survey were followed up one and a half years later. All samples were also processed by RT-PCR assay for CHIK Envelope (E) 1 gene. Immature mosquitoes were collected, link reared and identified with standard keys. Virus incrimination studies were done on Aedes aegypti and Ae. albopictus mosquitoes collected during the survey. RESULTS: Fever, headache and joint pain were the primary clinical presentations. Twenty three (35.93 %) of 64 samples reported during the outbreak were IgM positive for CHIK. Three samples showed PCR amplification. All these were IgM positive. The sequenced E1 gene revealed that the strains belonged to East Central South African (ECSA) genotype. INTERPRETATION & CONCLUSIONS: Field survey done after four months revealed that some individuals still had joint pain associated with episodes of headache and fever. It could be inferred that these persons might have contracted infection during the CHIK outbreak four months ago or during the intervening period which caused persistence of sequelae. ECSA genotype was found to be involved in the outbreak. Aedes albopictus was the predominant mosquito species collected during the outbreak.

Characterization of Japanese encephalitis virus (JEV) genotype III clinical isolates in northeast India.

BACKGROUND: Japanese encephalitis virus (JEV) is one of the major etiological agents responsible for causing large numbers of acute encephalitis syndrome (AES) cases in the northeastern region of India. This study was carried out to establish and characterize the circulating strain of JEV in the region in order to understand the disease epidemiology. METHODS: Virus isolation was attempted from 121 patients that presented with AES. Phylogenetic analysis was done using the Kimura-2-Parameter model based on envelope and pre-membrane gene sequence. A pathogenecity study was done in the Swiss albino mice model and assessed by Kaplan-Meier survival analysis. RESULTS: The phylogenetic analysis of the two JEV isolates obtained placed them within genotype (G)III, where they form a subclade within the Vellore group of Indian JEV strains. Neutralization assays suggested similarity between the study isolates and prototype Vellore JEV strain P20778. Pathogenesis in mice suggested that the circulating GIII JEV strains were neuroinvasive. CONCLUSIONS: This study showed that a pathogenic GIII JEV strain was circulating in the northeastern region of India. This finding is important as it is contrary to the belief that GI is gradually replacing GIII as the dominant genotype in Asia. GenBank accession numbers: HQ270470, JQ434468, HQ246155, JX018170.

Association of weather and anthropogenic factors for transmission of Japanese encephalitis in an endemic area of India.

Weather and anthropogenic factors are important determinants for Japanese encephalitis (JE) transmission. During 2008-2010, an increasing trend of JE was observed in Dibrugarh district of Northeast India. The JE cases were found to be clustered between June to October in each year. Monthly minimum temperature and rainfall were significantly associated with JE transmission at 1 and 2 months lagged. However, the relationship was more prominent at a lag of 1 month than that of two. Regression analysis suggested that rainfall, minimum and maximum temperature, and relative humidity at 6:00 h are significant predictors (P < 0.05) of quarterly occurrence of JE cases. Additional anthropogenic risk factors including the conditions such as pig sty/cattle shed around and lower part of the houses and proximity of rice field to the dwelling houses (P < 0.05) were also found to be predictors for JE occurrence. Meteorological and anthropogenic risk factors can be used to forecast JE outbreaks in Assam which in turn can help the local health authorities to protect communities in JE prone areas.

Clinical profile and outcome of Japanese encephalitis in children admitted with acute encephalitis syndrome.

Japanese encephalitis (JE) is an arthropod borne viral disease. Children are most commonly affected in Southeast Asian region showing symptoms of central nervous system with several complications and death. The clinical characteristics and outcomes in pediatric JE patients hospitalized with acute encephalitis syndrome (AES) are still poorly understood. A prospective study was conducted in pediatric ward of Assam Medical College Hospital to evaluate the clinical profile and outcome of JE in children. A total of 223 hospitalized AES cases were enrolled during March to December 2012. Serum and cerebro spinal fluids were tested for presence of JE specific IgM antibody. 67 (30%) were found to be JE positive. The most common presenting symptoms in JE patients were fever (100%), altered sensorium (83.58%), seizure (82.08%), headache (41.79%), and vomiting (29.85%). Signs of meningeal irritation were present in 55.22% of cases. Around 40.29%, JE patients had GCS ≤ 8. Among the JE patients, 14.7% died before discharge. The complete recoveries were observed in 63.9% of cases, while 21.3% had some sort of disability at the time of discharge. JE is still a major cause of AES in children in this part of India. These significant findings thus seek attentions of the global community to combat JE in children.

A comparison of clinical features of Japanese encephalitis virus infection in the adult and pediatric age group with Acute Encephalitis Syndrome.

BACKGROUND: Japanese encephalitis (JE) has traditionally been regarded as a disease of children. The age shift in JE patients in Assam, India in last few years has become a cause of concern. Comparison on clinical features of adult and pediatric JE patients has not been evaluated. OBJECTIVE: To compare clinical features of adult and pediatric with JE virus infection. STUDY DESIGN: From January 2008 to January 2010, 550 hospitalized patients with Acute Encephalitis Syndrome were enrolled. 259 (47.1%) were serologically confirmed as JE of which 66.4% were adult and 33.6% were pediatric. Data extracted from these patients were analyzed. RESULTS: Fever was the most common symptom in both the adult and pediatric. When compared with adult, significantly higher percentage of pediatric had neck rigidity, convulsions, abnormal behavior, seizures and elevated aspartate transaminase (P<0.05). Serum bilirubin levels were higher in 2.3% of adult but normal in all the pediatric. We found significantly higher mean elevated level of protein and WBC in CSF in adult (P<0.001) and mean elevated aspartate transaminase level (P<0.001) in pediatrics. There was no difference in mortality rate between pediatric and adult (8.2% vs. 4.4%, P=0.647). CONCLUSIONS: This study provides some significant differences in clinical features of pediatric and adult with JE. Age shift may be due to the invasion of the disease into new demography or some change in the virus strain over time. The Government of India has initiated an adult JE vaccination programme for the first time in Assam in 2011.

The effect of insecticide-treated mosquito nets (ITMNs) on Japanese encephalitis virus seroconversion in pigs and humans.

The effect of insecticide-treated mosquito nets (ITMNs) on Japanese Encephalitis (JE) virus seroconversion in pigs and humans was studied in Assam, Northeast India. A sharp reduction of seroconversion rate in human and pig was found in treated localities after intervention. A marked reduction was achieved in humans (risk ratio [RR] = 0.28, 95% confidence interval [CI] = 0.16-0.49) and pigs (RR = 0.21, CI = 0.11-0.40) in the Kollolua locality where ITMNs were used on both humans and pigs compared with the other two area, Athabari and Rajmai, where ITMNs were covering only either humans or pigs. Monitoring of the mosquito population in and around cattle sheds during dusk revealed no significant decline (P > 0.05) of vector density during the post-intervention period in study localities. In spite of the high preponderance of potential JE vector outdoors during the post-intervention period, an encouraging line of defense against circulation of JE virus through the use of ITMNs can be achieved in endemic areas.