Japanese encephalitis: a review of the Indian perspective

Japanese encephalitis virus (JEV) causes Japanese encephalitis, which is a leading form of viral encephalitis in Asia, with around 50,000 cases and 10,000 deaths per year in children below 15 years of age. The JEV has shown a tendency to extend to other geographic regions. Case fatality averages 30% and a high percentage of the survivors are left with permanent neuropsychiatric sequelae. Currently, there is no cure for JEV, and treatment is mainly supportive. Patients are not infectious, but should avoid further mosquito bites. A number of antiviral agents have been investigated; however, none of these have convincingly been shown to improve the outcome of JEV. In this review, the current knowledge of the epidemiology and the pathogenesis of this deadly disease have been summarized.

Bellary, India achieves negligible case fatality due to Japanese encephalitis despite no vaccination: an outbreak investigation in 2004.

OBJECTIVE: To confirm the existence of the outbreak of suspected Japanese encephalitis, identify the source, to understand the circumstances due to which the outbreak was taking place and to suggest measures for its control. METHODS: The team visited Bellary from 4th to 10th Sept, 2004. The team interviewed the key persons and analyzed the records at District Surveillance Unit and Entomological Surveillance Unit and case records of suspected JE cases admitted in Encephalitis ward in Vijay Nagar Institute of Medical Sciences (VIMS). Eco-entomological survey was done in houses and surroundings of 3 randomly selected cases of Encephalitis in rural and urban areas of District Bellary. Their family members and neighbors were also asked for the awareness and presence of disease. Data was analyzed for epidemiological and clinical profiles. RESULTS: The suspected JE cases were being reported from end of June 2004. The cases were sporadic and out of 34 cases reported to VIMS (till 10th of September), 32 were from Bellary district and 2 were from adjoining Andhra Pradesh. Among these 32, 22 were from Bellary Taluk, which in turn were mainly concentrated (10 were reported) in urban Bellary. The case fatality rate was zero as no death was reported. Entomological surveillance (done by District Surveillance Unit) revealed a high outdoor presence of Culex tritaeniorhynchus as well as an indoor rising density of this mosquito from 2 per man hour catch in January to 22 in the month of August in the affected villages. On the contrary, the investigations on 7th and 8th September revealed high densities of An.subpictus and An. peditaenatus and nil of Culex species in the urban areas. Amplifier host of pigs and water birds were occasionally sighted in the area. CONCLUSION: A good community awareness of encephalitis, a prompt referral system and a good supportive treatment for the patients and a good surveillance system and response were observed. Very close proximity with amplifying hosts of pigs was avoided by the community, though piggeries were still not very far away (1-3 Km). These may explain the reduction in cases, deaths and disabilities due to this disease in this district over the years. Possibilities of mutant strain which is less virulent and/or a better immune status of at risk population may also need to be explored. The impact of the mass vaccination with SA 14-14-2, imported from China in Bellary during July, 2006 remains to be evaluated. This will further decrease the case load.

Use of IgM-capture ELISA for confirmation of Japanese encephalitis infections in the Philippines.

In 2001, the Research and Biotechnology Division (RBD) of St Luke's Medical Center, in collaboration with the Institute of Tropical Medicine of Nagasaki University in Japan, initiated a long-term study of Japanese encephalitis in the Philippines. Laboratory confirmation of acute cases of Japanese. encephalitis was done by IgM-capture ELISA, which detects anti-JEV immunoglobulin M in cerebrospinal fluid (CSF) samples. In the period 2002-2004, a total of 614 CSF samples were submitted to RBD, and of these, 11.7% were positive for anti-JEV IgM: 17 in 2002, 18 in 2003, 32 in 2004, and 5 in 2005. Positive cases came from patients aged 2-77 years. In the 72 positive cases where gender was identified, 44 were male and 28 female. Possible co-infections with dengue virus were also detected by separate testing for anti-dengue IgM by ELISA in 17 CSF samples positive for JE.

Tropical infections in the ICU.

Certain arthropod-borne infections are common in tropical regions because of favorable climatic conditions. Water-borne infections like leptospirosis are common due to contamination of water especially during the monsoon floods. Infections like malaria, leptospirosis, dengue fever and typhus sometimes cause life threatening organ dysfunction and have several overlapping features. Most patients present with classicial clinical syndromes: fever and thrombocytopenia are common in dengue, malaria and leptospirosis; coagulopathy is frequent in leptospirosis and viral hepatitis. Hepatorenal syndrome is seen in leptospirosis, falciparum malaria and scrub typhus. The pulmonary renal syndrome is caused by falciparium malaria, leptospirosis, Hantavirus infection and scrub typhus. Fever with altered mental status is produced by bacterial meningitis, Japanese B encephalitis, cerebral malarial, typhoid encephalopathy and fulminant hepatic failure due to viral hepatitis. Subtle differences in features of the organ failure exist among these infections. The diagnosis in some of these diseases is made by demonstration of antibodies in serum, and these may be negative in the first week of the illness. Hence empiric therapy for more than one disorder may be justified in a small proportion of cases. In addition to specific anti-infective therapy, management of organ dysfunction includes use of mechanical ventilation, vasopressor drugs, continuous renal replacement therapy and blood products. Timely transfer of these patients to well-equipped ICUs with experience in managing these cases can considerably decrease mortality and morbidity.

Bilateral intracerebral haemorrhages: an atypical presentation of Japanese encephalitis.

Japanese encephalitis is common human endemic encephalitis seen over various parts of the world. Usual presenting features include an encephalitic syndrome, symptoms of frontal lobe, basal ganglia and thalamic involvement. Characteristic radiological picture is bilateral thalamic and basal ganglia hypo density in the CT scan and hypo-intensity in T1 and hyperintensity in T2 weighted image in MRI. Very rarely occurrence of bilateral hemorrhage may be seen in these regions. This radiological change may be early indicator of the disease before serological confirmation by the available diagnostic modalities. In this communication, we have reported a case of Japanese encephalitis presented with bilateral basal ganglia hemorrhages.

Japanese encephalitis in India: an overview.

Japanese encephalitis (JE)-epidemics have been reported in many parts of the country. The incidence has been reported to be high among pediatric group with high mortality. The incidence of JE in recent times is showing an increasing trend. It appears that JE may become one of the major public health problems in India, considering the quantum of the vulnerable pediatric population, the proportion of JEV infections among the encephalitic children and wide scattering of JE-prone areas. JE burden can be estimated satisfactorily to some extend by strengthening diagnostic facilities for JE confirmation in hospitals and by maintenance of contact with the nearby referral hospitals to collect the particulars on JE cases. Vaccination proves to be the best to protect the individual against any disease. In the case of JE, it is essential to immunize the pigs (amplifying host) also to interrupt the transmission of the disease.

Japanese encephalitis globally and in India.

Japanese encephalitis is demonstrated to be a significant public health problem in India and throughout Asia. JE primarily affects children between the ages of one and 15 years. Of those who contract the disease, approximately 70% either die or are left with a long-term neurological disability. JE vaccines have existed for a very long time, however due to cost and unstable supply, they have not been able to meet the needs of developing country health systems. In addition, alternative JE control measures have proven insufficient to control disease. As a result, 68 percent of babies born in the poorest countries of Asia are at risk for JE. Against this background, future directions for JE activities in India include control through vaccination when an affordable vaccine is available (at risk areas), strengthening surveillance data on disease patterns including age and geographic distribution, involvement of the private sector and incorporation of newer diagnostics as they become available and to focus on control efforts and prevent this debilitating disease now and in the future. Recent work, both internationally and in India, offers hope to help solve this public health problem and protect children from this disease.

TaqMan reverse transcription polymerase chain reaction for the detection of Japanese encephalitis virus

One step TaqMan reverse transcription polymerase chain reaction (RT-PCR) using TaqMan probe was developed for detection of Japanese encephalitis virus (JEV). Real-time RT-PCR was optimized to quantify JEV using the detection system (Rotor Gene 2000 detector) and dual-labeled fluorogenic probes. The gene specific labeled fluorogenic probe for the 3' non-translated region (3' NTR) was used to detect JEV. When the specificity of the assay using specific JEV primers was evaluated by testing three different JEV strains, other swine viruses and bovine viral diarrhea virus, no cross-reactions were detected with non-JE reference viruses. A single tube TaqMan assay was shown to be 10-fold more sensitive than the conventional two-step RT-PCR method. Detection limits of two step and real-time RT-PCR for JEV were 112 TCID50 /ml and 11.2 TCID50 /ml, respectively. Quantification of JEV was accomplished by a standard curve plotting cycle threshold values (Ct ) versus infectivity titer. Real-time RT-PCR assay using single tube method could be used as a sensitive diagnostic test, and supplied the results in real time for detection and quantification of JEV. We could detect JEV RNA genome in plasma samples of pigs inoculated with KV1899 strain at 2 days post inoculation, but couldn't in 41 fetus samples. This assay was sensitive, specific, rapid and quantitative for the detection of JEV from laboratory and field samples.

A long-term study on vector abundance & seasonal prevalence in relation to the occurrence of Japanese encephalitis in Gorakhpur district, Uttar Pradesh.

BACKGROUND & OBJECTIVES: Japanese encephalitis (JE) virus is an important cause of viral encephalitis in Gorakhpur district, UP. The area has been experiencing outbreaks of JE since 1978. No in-depth longitudinal studies have been carried out on the mosquito species, particularly JE vectors prevailing in the area. Entomological studies were carried out in the district in order to determine the species composition, relative abundance and seasonal prevalence of mosquitoes in relation to the incidence of JE. METHODS: Three JE affected villages were selected as study sites. Weekly visits were made to each village and mosquito collections were made in and around the pig enclosures and cattle sheds with the help of mouth aspirators, aided by flash lights at dusk. RESULTS: The overall mosquito population showed a bimodal pattern with short and tall peaks during March and September respectively. Based on the elevated density and infection with JE virus, Culex tritaeniorhynchus has been considered responsible for causing epidemics in the area. Cx. pseudovishnui, Cx. whitmorei, Cx. gelidus, Cx. epidesmus, Anopheles subpictus, An. peditaeniatus and Mansonia uniformis are suspected to have played some role in the epidemiology of JE in the region. JE cases were reported between August and November with the peak in October when the vectors population, particularly Cx. tritaeniorhynchus was on the decline. INTERPRETATION & CONCLUSION: The results of the study indicate that Cx. tritaeniorhynchus, the most likely vector of JE together with other known vector species remained more active during the period of paddy cultivation. Integrated antilarval measures before the beginning of paddy irrigation may check the breeding of JE vectors in the paddy fields. It may prove beneficial in reducing the vector population during the JE transmission season.

Clinical outcome and neurological sequelae in serologically confirmed cases of Japanese encephalitis patients in Assam, India.

We report the clinical outcome and prognostic factors in 39 cases of childhood Japanese Encephalitis admitted to a tertiary hospital of Upper Assam and followed up for 421 days in the community. The mortality rate was 20.5% in our study. The mean GCS (9.97 +/- 0.91) was higher in surviving cases than the fatal cases (GCS 7.5 +/- 1.78) at admission. The fatal cases died within 4.75 +/- 3.19 days in the hospital. All the patients had low BMI (surviving cases 13.54 +/- 2.3; fatal cases 12.05 +/- 0.12) and were anemic. Cerebrospinal fluid (CSF) was clear in 91.4% cases but pressure and protein content were increased in all cases. About 10% cases had parkinsonian features at the time of discharge. Residual symptoms remained in about one third of cases even after 421 days.

Neurophysiological changes in Japanese encephalitis.

Japanese encephalitis (JE) is an encephalomyelitis involving cortex, subcortex, brainstem and spinal cord. There is paucity of studies on the neurophysiological evaluation in JE. This study aims at comprehensive evaluation of EEG, sensory and motor evoked potentials, nerve conduction and electromyography; and correlate these with clinical findings. Sixty five patients with JE diagnosed on the basis of clinical, radiological and virological criteria were subjected to a detailed clinical evaluation during the acute stage of illness. Cranial CT scan or MRI was carried out in all the patients. All the patients underwent 10 or 18 channel EEG, motor and sensory evoked potentials to both upper and lower limbs bilaterally as well as peroneal and sural nerve conductions and concentric needle EMG. Outcome, was defined at the end of 3 months into poor, partial and complete recovery. The patient's age ranged between 2-65 years. There were 40 males and 25 female patients. Fifteen patients were less than 12 years of age. History of seizure was present in 31 patients. Quadriplegia was seen in 39 and hemiplegia in 8 patients. Muscle wasting was present in 16 patients and tendon reflexes were reduced in 12 and of mixed pattern in 14 patients. Cranial MRI revealed thalamic lesion in 38, basal ganglia in 21, substantia nigra in 30, pons in 5, cerebellum in 3 and cerebral cortex in 7 patients out of 57 patients. EEG revealed nonspecific theta to delta slowing in 45, alpha pattern coma in 5 and epileptiform discharges in 8 patients. EMG revealed fibrillations in 23 patients. Motor evoked potentials were abnormal in 34 out of 46 patients and revealed patchy and focal abnormalities comprising of unrecordable, prolonged and normal pattern. Somatosensory evoked potentials were abnormal in 8 patients only. At 3 month, 26 patients had complete, 13 partial and 15 had poor outcome. Eight patients died in acute stage and 3 were lost to followup. MEP correlated with weakness and 3 month outcome whereas EEG, SEP and EMG did not have any correlation. MEP changes were more frequent in JE and had prognostic significance.

Japanese encephalitis with movement disorder and atypical magnetic resonance imaging.

With the advent of magnetic resonance imaging, brain lesions associated with Japanese encephalitis are increasingly being recognized and correlated with movement disorder. Bilateral haemorrhagic thalamic infarcts on MRI, suggested as a characteristic finding in Japanese encephalitis were conspicuous by their absence in this case report of Japanese encephalitis.

The first report on human cases serologically diagnosed as Japanese encephalitis in Indonesia.

Although Japanese encephalitis (JE) virus was isolated from mosquitos in 1974, human JE cases have never been reported in Indonesia in spite of the prevalence of anti-JE antibodies among human and pig populations as well as abundant JE vector mosquitos. In this report, we describe serological diagnosis of JE cases in Bali. Indonesia. using IgM-capture ELISA both on serum and cerebrospinal fluid (CSF) of the patients. In the first series of our investigation (Series 1), we examined serum specimens from 12 patients with clinical diagnosis of viral encephalitis, meningitis or dengue hemorrhagic fever (DHF), and found 2 possible JE cases. In the next series (Series 2), we examined both serum and CSF from encephalitis patients and gave laboratory diagnosis of JE. One of them was suspected to have concomitant or recent infection with dengue virus, probably type 3. These results strongly indicated that JE has been prevalent in Bali, Indonesia.

Investigation of an epidemic of Reye's syndrome in northern region of India.

OBJECTIVE: To determine the extent, epidemiological and clinical features of an epidemic of non-inflammatory encephalopathy in northern region of India. DESIGN: Surveillance of referred cases having unconsciousness after a short bout of fever during October and November 1997. Case control study in 7 most affected villages. METHODS: Active case finding was done to assess the extent and severity of the epidemic by interviewing health professionals and by reviewing mortality records in 10 districts of Haryana, Punjab and Chandigarh. A house to house survey was conducted in seven most affected villages. A case was defined as any child of less than 15 years of age, who had prodromal fever followed by vomiting and unconsciousness with subsequent recovery or death. Two age and sex matched controls who had fever without unconsciousness were taken for each case, one from nearby house and another staying furthest from the affected house. These groups were compared for various epidemiologic factors, clinical features and treatment pattern. Residual medicines used by affected patients were tested for presence of salicylate. Local village practitioners were interviewed for their knowledge and attitude towards use of aspirin in a febrile child. RESULTS: Information regarding 129 affected children (M: F=1 : 1) could be obtained. Age ranged between 1 to 12 years (mean 5.8 years). Most were from rural or semi-suburban areas. Attack rate was 5.4/1000 and case fatality rate was 72%. Multiple sibs were affected in 9.3%. History of fever was reported by 83%, vomiting preceding unconsciousness by 83% and abnormal behavior by 65%. Abnormal posturing was reported in 55%. Seventeen (61%) of 28 samples had IgM antibodies in serum/CSF against measles. Twelve (36%) of 33 serum samples tested positive for Varicella zoster virus. None gave history of aspirin intake and 10 samples of residual drugs did not contain salicylate. However, 6 out of 19 blood samples taken from affected patients contained salicylate. Environmental factors were in favor of Japanese encephalitis (JE) but brain biopsy and serology disproved it. Based on earlier report of JE from this area, the cases in present epidemic were being reported as JE before this study was undertaken. Intensive fogging with malathion was being undertaken as antimosquito measure, specially around the affected houses. Local village practitioners (n = 37) were unaware of contraindications of aspirin in a febrile child. CONCLUSION: Measles and varicella zoster emerged as the probable etiologies for the viral prodrome precipitating these cases of Reye's syndrome. Aspirin might have a contributory role. Malathion is another putative cofactor.

Viral encephalitis of public health significance in India: current status.

Japanese encephalitis (JE) and rabies are 2 viral encephalitis that are of public health importance in India. JE is a zoonosis with the primary cycle occurring in arthropods (mosquito vectors) and vertebrate animals (primarily the pig), man being only an incidental 'dead end' host. Out-breaks have been seen in most parts of India except the north west. The disease presents with a prodromal stage, an acute encephalitic stage with coma, convulsions and variable deficits and a convalescent stage. Diagnosis can be made by viral isolation from CSF or brain, or serologic tests such as haemagglutination inhibition test and IgM antibody capture ELISA in CSF and blood. There is no specific treatment. Mortality ranges from 20-50% and almost half the survivors have sequelae. The most effective control measure besides control of mosquitos is vaccination. A killed mouse brain vaccine is being prepared in India and is safe and effective but expensive. Rabies is a highly fatal encephalomyelitis primarily occurring in urban dogs and wild animals especially canines. It is endemic in India and affects an estimated 3 per 100,000 persons annually. The patient initially may display bizarre combative behaviour. The disease can be effectively prevented by post exposure vaccination. The nervous tissue vaccine is no longer recommended because of unacceptable neurotoxicity. Three cell culture vaccines are presently available with about equal efficacy.

Japanese encephalitis in India.

Japanese encephalitis (JE), caused by a mosquito-borne virus was first recognised in India in 1955 and since then many major out-breaks from different parts of the country have been reported, predominantly in rural areas. Children are mainly affected, with morbidity rate estimated at 0.30 to 1.5 per 100,000 population. Case fatality rate has ranged from 10% to 60%, and up to 50% of those who recover may be left with neurological deficits. Reported incidence has generally been higher in males than in females, but subclinical infections have occurred equally in both sexes. A large number of subclinical infections occur each year during the transmission season. Diagnosis at the primary health centre (PHC) level is based on clinical symptoms only. Therefore, there is a need to develop simple tests for use at the peripheral level both for diagnosis and for epidemiological surveys. JE is a vaccine preventable disease, but there are many logistic problems for effective implementation of vaccination.

Eighth nerve involvement in meningo-encephalitis.

Seventy-two patients suffering from meningo-encephalitis were studied, clinically, biochemically, microbiologically and virologically. Evidence of rising titre in serum and CSF of antibodies to Japanese encephalitis were present in 50% of cases, and recent past infection in 20% of cases. Cranial nerve involvement particularly the "8th" was present in 70% of cases though there was a 2.5% involvement of the 2nd, 3rd and 6th nerves. All the patients belonged to plain Tribal population and all had a history of eating pork 7-10 days prior to development of the infection.