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Brief Reports Indian Pediatrics 2002; 39:1143-1148 |
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Clinical Outcome and Neurological Sequelae in Serologically Confirmed Cases of Japanese Encephalitis Patients in Assam, India |
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Japanese encephalitis (JE) is a vector borne zoonotic viral infection, reported from many countries, including India(1). In Assam, JE epidemics are occuring periodically since 1976 with high morbidity and mortality. The survivors may be left with permanent residual neurological abnormality, majority of the victims being children below 15 years(2). World Health Report of 1995 has indicated that 0.1 per 1,00,000 population may suffer from disability due to JE. Increased severity and susceptibility to the disease go hand in hand with poor nutritional status of the people(3), in countries like India. In JE, recovery from neurological deficits takes long time and some problems persist for couple of years(4). Due to unaffordable prolonged tertiary care in developing countries, JE patients are usually discharged from the hospital after recovering from acute phase. In these cases subsequent long-term consultation with specialists is very difficult, especially in the northeastern part of India where surface communication is poor. Usually the cases are lost after discharge from the hospital. Hence the knowledge about the profile of neurological sequelae, recovery or persistence of deficits is essential to plan domestic care strategy. This study was undertaken to have baseline information about the clinical course of these patients after discharge in the context of a remote area. Subjects and Methods Children aged between 3 to 12 years, admitted to pediatric ward of Assam Medical College and Hospital, Dibrugarh and Tata Referral Hospital, Chabua, Dibrugarh, during July-August, 1998, having typical clinical features of encephalitis (sudden onset of high fever, headache, vomiting, convulsion, behavioral disturbances, altered conscious-ness, neck rigidity and motor deficit) and confirmed by serelogy (MAC ELISA) were included in the study. A total of 22 patients could be followed up till the end of the study. Routine laboratory investigations like total leukocyte count, differential leukocyte count, erythrocyte sedimentation rate, hemoglobin and cerebro-spinal fluid analysis were done as per the standard protocol of the hospital. However, demonstration of JE antibody in CSF could not be done. Malaria infection was excluded by epidemiological evidence, clinical criteria and peripheral blood film examination. MAC-ELISA test was carried out in serum within 1 week of admission, for JE/DEN using the test kits supplied by National Institute of Virology, Pune, India. Results were interpreted as per the cut off point formula given in the kit. In brief the following formula was used to calculate the result. Units = Optical density (OD) of sample - OD Negative control —————————————————————— × 100 OD weak Positive control - OD Negative control More than 50 units in test sample were considered positive for IgM antibody. Glasgow coma scale (GCS) was used to assess the level of consciousness. Standard techniques were employed for anthropometry. Socio-economic condition of the family was recorded on Kuppuswami scale(5). The investigators followed up cases and help of a psychiatrist was taken time to time. Statistical analysis was done by using students t-test and Mann-Whitney U test. Results Out of 39 patients initially included in the study, 23 (58.97%) were males and 16 (41.03%) females. Eight (20.51%) patients (male - 2 and female - 6) died in the hospital and 6 (15.38%) patients dropped out during the period of follow up and 3 who apparently recovered completely at the time of discharge also did not cooperate subsequently. In these cases initial monitoring was done daily in the hospital. After discharge patients were examined monthly for 2 months, 2 monthly for 8 months and 3 monthly for rest of the days up to 421 days. Table I- Comparative Clinical Status of Fatal and Surviving Cases at Onset and During Admission
It was observed that all suspected JE patients, reported to the hospital between 3 to 6 days after the onset. However, the surviving cases, reported early (3.19 ± 0.7 days) in comparison to the fatal cases (5.0 ± 1.18 days) (P = 0.003, t = 4.15). Further, the mean GCS (9.97 ± 0.91) was higher in surviving cases than the fatal cases (GCS 7.5 ± 1.78) at admission. The mean duration of hospital stay of 8 fatal cases was 4.75 ± 3.19 days. Most of the patients (84.6%) were from poor families of rural area. All the patients had low body mass index (BMI) (surviving cases 13.54 ± 2.3; fatal cases 12.05 ± 0.12) and were anemic. The difference between mean hemoglobin level of fatal 6.16 ± 0.4 g/dL) and surviving cases (7.2 ± 1.5 g/dL) was significant (P = 0.002, t = 3.30) (Table I). Cerebrospinal fluids (CSF) was clear in 91.4% cases but pressure and protein content were increased in all cases. Total cell count in CSF varied from 5 to 85 cells/cu mm with lymphocytic predominance. Out of 30 patients, 13 (43.3%) showed complete recovery at the end of 421 days. Residual problems persisted in 9 cases till the end of study. Besides motor deficits, functional abnormalities like loss of recent and past memories, delayed reaction to verbal communications, failure to recognize the family members, lack of concentration, abnormal behavior, depression, agitation (mood disorder), fear, hyperactivity, non-cooperation, singing or talking alone were common. Cranial nerve palsy, gaze palsy, global aphasia, abnormal articulation and impaired hearing were less common findings. Parkinsonian features like expressionless face, soft rapid indistinct speech, flexed posture, muscle rigidity and intension tremor were present in three cases. However, rapid small step with tendency to run was observed only in two of them. Impaired bladder and bowel control was present in 3 patients at the time of discharge. Out of them one recovered after about one year. Initially, 2 cases had gaze palsy, but subsequently 2 more cases developed gaze palsy. Convulsive disorders, observed in 4 cases persisted up to 120 days of follow up but the duration of attack gradually decreased with increasing interval between two attacks. None of them reported convulsive episode during last four months of follow up. Episodic headache at different interval was a prominent feature, which kept on bothering 3 patients. Motor deficit, memory loss, intellectual deficit, mood disorders, and abnormality of speech were present in many cases at the initial phases of follow up, but most of them recovered with time. In contrast, cranial nerve palsy, autonomic disturbance, parkinsonian features and muscle pain, present in lesser number of patients initially, persisted till end. Improvement was seen up to 330 days. Afterwards most of the signs and symptoms were static (Table II). Table II- Clinical Symptoms and Signs of Japanese Encephalitis Cases at Various Times of Follow Up
Discussion Mortality (20.5%) in our series was lower than the series reported from other parts of India. Annual incidence of JE in India ranged from 1243 to 7500 (years 1978 to 2000) with average case fatality rate of 35.1% with highest during 1994 (51.5%) and lowest during 2000 (16.0%)(6). Worst affected states were Uttar Pradesh, Assam, Andhra Pradesh, Bihar, Haryana, Karnataka, Manipur, Tamil Nadu and West Bengal. During the study year (1998), case fatality rate (CFR) in India was 23.9%. The overall complete recovery rate was 43.3% in the present series. Studies conducted elsewhere(4) showed variable rates of recovery and recovery time. Studies conducted in Vietnam(7) showed 58% with left over sequalae at 45 days, in South India 70% cases were with residual deficit after 2 years(2,8) and in Karnataka moderate to severe sequalae were observed only in 28.82%(9). In an epidemiological analysis conducted by Regional Medical Research Centre for North Eastern Region of India (1980 to 1993), revealed the average case load in Assam to be 295.5 ± 364.17 per year and the case fatality ratio 40.9 ± 10.95(10). However, these data were based on clinical and epidemiological diagnosis. Hence the exact comparison with the present study is difficult. All the patients were anemic and with low BMI at admission. There was no significant difference of BMI between the fatal and surviving cases. Hence, nutritional status might not be directly related to the case fatality in our series but it might have contributed to the overall susceptibility of the cases. However low hemoglobin status in fatal cases needs further study. It was observed that, fatal cases uniformly reported late to the nearest medical facility in comparison to the cases that recovered with or without neurological sequelae. In JE infection cell reactions become more intense from fourth day onwards and along with it, necrolytic areas appear in fatal cases. However, when the patient survives for more than 10 days, cell response reduces in severity with persistence of necrolytic lesion(2). Perhaps, proper hospital care at initial few days plays a crucial role in survival of JE patients. Further, most of the cases in our series were coming from familities with poor socio economic status and low literacy rates of parents. Therefore, children were brought to the doctors only when sufficiently severe symptoms are noticed. This may be the cause of high mortality among these patients. Parkinsonian features in JE cases are rare sequelae, caused due to involvement of substantia nigra in brain(2,11). In our series about 10% cases had parkinsonian features at the time of discharge. Though these symptoms improve with time(2,4), yet in our patients only one out of 3 showed improvement. Two cases had recurrence of high fever, loss of speech, and convulsion after 2 months of follow up. After this episode they developed gaze pasly. Hence, number of gaze palsy cases increased to four. Etiology of this recurrent episodes could not be ascertained; whether they are of JE origin or otherwise. Clinically these cases appeared to be of Japanese encephalitis and re-infection at such a short interval is a remote possibility. Persistence of JE virus after Japanese encephalitis has been reported(12). These persistent JE virus getting reactivated and giving rise to such symptoms cannot be ruled out. However, at the same time in absence of isolation of virus, molecular evidence or other elaborate serological procedure, latency and reactivation of virus could not be ascertained. Cases with paralysis though improved during follow up, yet with starting of activity, they developed muscle pain, which added to the list of their misery. Hence the appearance of muscle pain was late and perhaps related to the recovery phase of paralysed muscles. It is evident from the study that many patients suffer from disabilities for different duration after encephalitis. Unless they get sufficient domestic care after encephalitis, their misery will be multiplied to several folds. This indicates need of training to the family members in this area. Acknowledgement Authors are thankful to The Director, National Institute of Virology, Pune, for supplying the Mac ELISA test kits. Dr. A.C. Phukan, Dr. (Mrs.) M. Hazarika, Dr. S. Ghosh and Mrs. M. Goswami Sharma are gratefully acknowledged for their help. Mr. D.K. Pegu and Mr. Punannanda Gogoi are thankfully acknowledged for technical help. Contributors: HCB was responsible for follow up of cases, acted as a team leader in the field and carried out virological tests. DB conducted clinical examination of cases in field and helped in testing the samples. DP was the clinician-in-charge of hospitalized cases and was responsible for management and initial studies in these cases. HCB, DB and DP wrote the manuscript. JM conceived, planned and supervised the study, corrected the manuscript and will act as guarantor for the paper. Funding: ICMR intra-mural fund. Competing interests: None stated.
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