|DR. B. C. DASGUPTA MEMORIAL ORATION
|Year : 2014 | Volume
| Issue : 3 | Page : 147-155
Whose failure? Encephalitis kills!
Nagabhushana Rao Potharaju
Consultant, Japanese Encephalitis Projects, PATH; Chairman, AES/JE Expert Committee, Uttar Pradesh, Team Leader and Facilitator, Joint Monitoring Mission of Government of India and World Health Organization 2014; Former Professor and Head of the Department of Neurology/Pediatric Neurology, Osmania Medical College/Niloufer Hospital/Osmania General Hospital, Hyderabad, Telangana, India
|Date of Web Publication||13-Aug-2014|
Dr. Nagabhushana Rao Potharaju
10-3-185, St. John's Road, Secunderabad - 500 025, Telangana State
Source of Support: Program for Appropriate Technology in Health (PATH), World Health Organization, Government of India, Environmental Health Project (EHP) for BBIN (Bangladesh, Bhutan, India, Nepal), Government of Andhra Pradesh., Conflict of Interest: None
| Abstract|| |
Encephalitis continues to be one of the most dreaded diagnoses because a high rate of morbidity and mortality are accepted even before starting the treatment. Most encephalitis cases occur in rural areas due to poor environmental sanitation, high-vector density, shortage of protected water supplies and lack of health education. Vaccination, environmental sanitation, vector control, health education and attention to prompt diagnosis and treatment in rural hospitals are the four essential pillars for reducing case fatality rate (CFR) of encephalitis. Frequently, virulence of the virus, immunological state of the host, unavailability of antiviral drugs and lack of enough tertiary care hospitals (TCH) are not responsible for the high CFR. Basic supportive care is not being practiced meticulously in Primary and Secondary Care Hospitals (PSCH), and their services are not being utilized fully. Main causes of high mortality and morbidity rates are hypoxia and ischemia of brain and other organs precipitated by preventable, controllable or treatable complications due to lack of basic medical and nursing care during transport to the TCH. Undiagnosed Rickettsial infections are suspected to be partly responsible for the high CFR in some areas. Improving rural hospitals and their ambulance services are the most economical way to reduce CFR. "Treatment facilities must be made available at places where cases occur." The best way to reduce CFR of encephalitis in developing and underdeveloped countries is to increase and improve PSCH and sensitize politicians, administrators, medical/nursing professionals and more importantly to impress and convince the public to utilize them.
Keywords: Acute encephalitis syndrome, case fatality rate, encephalitis, health care, India, Nepal, planning, primary care, public health, Rickettsia
|How to cite this article:|
Potharaju NR. Whose failure? Encephalitis kills!. Indian J Public Health 2014;58:147-55
| Introduction|| |
Encephalitis has been a challenge across the globe since a long time and reducing the number of deaths due to encephalitis was thought to be a mission impossible for every country.  Fever with altered sensorium and/or seizure is acute encephalitis syndrome (AES). World Health Organization (WHO) coined this new term for use during surveillance, so that even an inexperienced basic health worker will be able to identify a case.  Encephalitis is defined as inflammation of the brain, caused by direct infection or a hyper-sensitivity reaction to a pathogen or foreign protein. Clinically, presence of focal signs (paralysis or abnormal movement) indicates direct involvement of brain (encephalitis) and absence of focal signs indicates extra cerebral causes (encephalopathy).
Approximately, three billion people live in endemic regions and 375 million population is at risk of developing AES in India [Figure 1].  World's first and only population-based study of AES showed that the incidence rate (IR) for India is 0.46, and for Nepal 5.75.  Japanese encephalitis (JE)/AES was reported from 179 endemic districts in 20 states of India, of which about 39% disease burden is in Assam, 24% in Bihar, 21% in West Bengal and 14% in Uttar Pradesh in 2014 till 31st July, 2014.  Almost 80% of the cases occur before the age of 19 years. Most encephalitis cases occur in rural areas due to poor environmental sanitation, high-vector density, shortage of protected water supplies and lack of health education.  JE virus is a leading cause of encephalitis, causing an estimated 67,900 JE cases annually  and is a major cause of childhood mortality and morbidity in countries of Southeast Asia and Western Pacific regions. JE virus cannot be eradicated because of its extensive prevalence among birds and animals. The high-case fatality rate (CFR) (20%-30%) and frequent residual neuropsychiatric damage in survivors (50-70%) make JE a major public health problem. 
|Figure 1: Acute encephalitis syndrome in India and Nepal. Modified with permission|
Click here to view
| Etiology|| |
Over 100 different pathogens (viruses, bacteria, fungi, parasites, spirochetes, etc.,) cause AES. A specific etiology of AES is determined in only 25% of the cases. Of these cases, 10-15% are caused by JE and 10-15% are caused by other pathogens such as enteroviruses (EV-71, EV-75, EV-76 and EV-89), coxsackievirus B5, echovirus 19, measles, mumps, rubella, rabies, Nipah virus, dengue, chikungunya, West Nile virus, cytomegalovirus, varicella-zoster, Ebstein-barre virus, influenza, adeno virus, rickettsia, mycoplasma pneumonia, acute disseminated encephalomyelitis, etc.  Herpes simplex encephalitis is the commonest sporadic cause of encephalitis. Approximately, 75% had no identifiable etiology. ,,,, 90% of AES cases have no specific treatment (e.g., antiviral medicines). 
Repeated outbreaks were reported from 12 States and Union Territories in India like Uttar Pradesh, West Bengal, Karnataka, Assam, Tamil Nadu, Kerala, Bihar, Haryana, Maharashtra and Goa. During the last decade, 2000-5000 cases have been recorded with a CFR decreasing from 25% to 10-15%. Although JE has traditionally been regarded as a children's disease, the majority of cases now occur in adults in countries where strong immunization programs exist.  During the last JE epidemic in Assam in 2013, adults contributed to 70% of cases with a CFR of 26.5. Adult cases are being reported from Uttar Pradesh, Bihar, Assam and West Bengal. Adults are not protected by the current immunization program, probably because of waning immunity.  Assam is the first state in India to administer JE vaccination to adults.  Nepal already undertook JE vaccination of adults. 
Recurrent massive outbreaks of AES epidemics have been attacking Uttar Pradesh and other northern states of India with high morbidity and mortality since 2005. In Uttar Pradesh >50,000 died due to AES in the last 30 years. Consistent efforts have been made both by the state government of Uttar Pradesh and Government of India such as vaccination against JE, environmental management, larval control, pig control, provision of India Mark II hand pumps and deep wells to counter enteroviral infections; however, the burden of AES cases has not reduced significantly.  The government of Uttar Pradesh has made steadfast efforts in strengthening tertiary care hospitals (TCH) in Lucknow, Aligarh, Allahabad, Banaras, Gorakhpur, Jhansi, Meerut, Kanpur, Saifaj, Agra and Bareilly. BRD Medical College Hospital in Gorakhpur with its highly specialized equipment and a special JE and AES ward has earned a good name in the management of encephalitis and attracts almost 90% cases from eastern Uttar Pradesh. Due to the highly publicized media coverage of the facilities provided at BRD Medical College, the communities from nearby districts of Uttar Pradesh., Bihar and Nepal prefer to seek treatment there. In addition, due to limited facilities and manpower at the Primary and Secondary Care Hospitals (PSCH), the work load on BRD Medical College is very high. Improving the TCH in Uttar Pradesh has not reduced the CFR.  Rickettsial infections (RI) are suspected to be partly responsible. 
| Causes of High Case Fatality Rate|| |
Encephalitis continues to be one of the most feared diagnoses because the high rates of morbidity and mortality are accepted even before starting the treatment. CFR of AES according to older statistics followed the rule of thirds (33.3% die; 33.3% have sequelae, and 33.3% survive without sequelae). Frequently, virulence of the virus, immunological state of the host, unavailability of antiviral drugs and lack of enough TCH are not responsible for the high CFR. Basic supportive care is not being practiced meticulously in PSCH, and their services are not being utilized fully.  Undiagnosed RI are suspected to be partly responsible for the high CFR in some areas .
One incidental observation in 1995 in India  changed the outcome of encephalitis. Out of 1500 deaths analyzed, 91.27% of the patients traveled for >1 h during which supportive care and symptomatic treatment were not appropriately provided. Main causes of mortality and morbidity were mostly preventable namely, hypoxia, pulmonary aspiration of saliva or vomiting, secondary bacterial infections, status epilepticus, pulmonary infections, raised intracranial tension, hypoglycemia, stress ulcers and gastric hemorrhage, hyperpyrexia, brainstem involvement, airway block by the secretions, bedsores, pulmonary edema, hypotension, thromboembolism, syndrome of inappropriate anti-diuretic hormone secretion and corneal ulceration. >93% deaths occurred between 2 am and 4 am. A possible contributing factor for these deaths could be that if the child did not look critically ill during the early hours of the night, the child was not monitored closely and so, symptoms suggestive of aspiration or status epilepticus were not picked up immediately and managed. ,, More than 80% deaths and >88% of the complications/sequel could have been prevented by the timely provision of symptomatic treatment. ,,, What was seen in Niloufer hospital of Hyderabad, India , was later proved in various states of India and a country like Nepal [Figure 2].  This observation  was followed by an 18-year population-based study of encephalitis in Uttar Pradesh, India and Nepal  which has conclusively shown a simple and doable way to reduce deaths (to <1%) , and morbidity even in developing and underdeveloped countries without any significant additional finances or staff. Simple clinical findings and investigations aid in the differential diagnosis and correct management of AES. ,,, Simple ways to reduce morbidity and mortality are turning the patient to one side (to prevent aspiration), keeping the airway clean, administration of oxygen; maintaining body temperature, glucose and blood pressure level; urinary catheterization, protecting the eyes, avoiding unnecessary stimulation of the patient, oral hygiene, starting oral nutrition at the earliest, bowel care, physiotherapy; promptly treating seizures, pain and cerebral edema; judiciously using drugs, prompt treatment of sequel and timely referral to a higher center if a complication develops. ,,,,
| Whose Failure?|| |
Recently, it has been proved by many states in India and Nepal that CFR can be reduced even to zero with inexpensive measures. , Bihar, Uttar Pradesh and Assam states of India regularly report high CFR [Figure 3]. High CFR is multifactorial as follows and factors are mostly preventable, controllable or treatable.
Without the knowledge of correct DB, planning and allotment of adequate finances/staff are impossible and will lead to increased CFR. Reasons for this are many.
Acute encephalitis syndrome not reported
Many States/Union Territories in India and many districts in Nepal have not reported any AES so far [Figure 1]. The states of India that did not report AES were Arunachal Pradesh, Chhattisgarh, Gujarat, Himachal Pradesh, Jammu and Kashmir, Madhya Pradesh, Meghalaya, Mizoram, Odisha, Rajasthan, and Sikkim. The Union Territories of India that did not report even one case of AES are Andaman and Nicobar Islands, Chandigarh, Dadra and Nagar Haveli, Daman and Diu and Puducherry.  Many districts of Nepal like Taplejung, Manang, Mustang, Jajarkot, Jumla, Mugu, Bajhang, Bajura, Darchula and Doti have not reported any AES.  The question that haunts us is whether the surveillance is active at all in these states/districts. Nonexistence of a performance target (PT) for AES is an important reason for apparently low IR in India. National Vector Borne Disease Control Program (NVBDCP) coordinates its work with the health ministries of various states. Whatever reports are submitted by the state are accepted and recorded by the NVBDCP. Doctors are scared to diagnose a case as AES in many states. Most private hospitals, especially in the corporate sector, do not report AES, and no action is taken against them. Since private nursing homes are under the control of District Medical and Health officers (DMHOs), they are threatened with dire consequences by the DMHOs if AES case is reported from their nursing home because any AES incidence is interpreted as DMHOs inefficiency. In Nepal, there is a complementary surveillance mechanism supported by the World Health Organization-Immunization Preventable Diseases (WHO-IPD), which made surveillance successful in >90% of the cases.  Bhutan did not report any AES/JE for long. After the convincement made by the author,  now Bhutan is reporting cases of AES/JE. A PT of 0.46 for IR of AES for India and 5.75 for Nepal is suggested to confirm that active surveillance exists.  Integrated Disease Surveillance Program collects data, but there is limited dissemination of information, including feed-back for those generating data. There is a critical need to strengthen surveillance, supervision and monitoring at all levels with regular meetings, verification of records, and definition of action points and follow-up of the implementation. A PT must be fixed to rectify the defects in surveillance. Using the current mean IR of AES as PT for the next year is simple and practical. 
At present, there is no cross-border reporting between neighboring countries  and various neighboring states of India. Surveillance information needs to be harmonized and shared between neighboring states/countries under Ministry of Health/Directorate of National Vector Borne Disease Controle umbrella, and a Memorandum of Understanding between countries/states needs to be in place.
Factors which increase the DB are:
- Overcrowding with resultant worsening of environmental sanitation and difficulty in getting protected water supply.
- Nonexistent or malfunctioning drainage systems both in the rural areas [Figure 4] and hospitals [Figure 5] of all levels is very frequent. Safe water is a rare commodity in rural areas [Figure 6].
|Figure 6: Overhead tank of drinking water in a district hospital. It has no lid|
Click here to view
- Biomedical Waste Management system is nonexistent in most of the hospitals [Figure 7].
Prevention of JE requires improved coverage of vaccination, improved habitation/segregation of pigs [Figure 8], vector surveillance/control and personnel protection measures.
Currently, vaccines are available for only a few diseases like JE, measles, mumps and rubella, etc.  Using vaccines judiciously in the endemic areas can bring down the DB and the resultant mortality.
Misdiagnosis and missed diagnosis are not rare. Atypical presentations, if investigated properly, may lead to new discoveries. During epidemics, management of hundreds of children and mass hysteria of their parents overloads the few rural basic doctors available.  To avoid media, bureaucratic, political and public criticism, sometimes, doctors make a diagnosis in a hurry and initiate some steps to show that they are controlling the epidemic and treating the cases. This results in the labeling any acute epidemic coma as epidemic encephalitis or Reye syndrome by the investigating doctors to tide over the crisis since other neurological diseases that can cause coma were never reported to have presented in an epidemic form.  "Paper publication syndrome"  led to the publication of papers with erroneous diagnosis of diseases such as atypical measles encephalitis,  and Chandipura encephalitis. ,, Misdiagnosis of epidemic brain attack as atypical measles encephalitis and Chandipura encephalitis, , and some RI as the enteroviral encephalitis led to mismanagement and higher CFR. , Missing the diagnosis of Nipah viral encephalitis costed India dearly in terms of morbidity and mortality. ,
The well-accepted principle that one epidemic has one cause is true only if all the investigating clinicians separate the epidemic cases. Analysis of few samples in outbreak situations will be diagnostic only if they actually represent the epidemic. Otherwise, they will be misleading. There are always multiple causes resulting in encephalitis at any given time. Because of the heavy workload, all cases presenting during a particular period are included as one epidemic and this confuses the final diagnosis and management.
Whenever a new diagnostic possibility is raised by a clinician, tests must be done on a priority to rule in or rule out the diagnosis. Sometimes tests with poor sensitivity and specificity are done to negate the diagnosis. When a senior or an institution misses the diagnosis and a junior or an individual makes the diagnosis, egoism delays the acceptance of the correct diagnosis. When different experts arrive at different diagnoses of the same epidemic, an expert committee must be formed including all the experts of both the groups. It must be ensured that all committee members attend all the meetings and draw conclusions within a month. Sometimes crucial decision can't be taken due to nonattendance of the member of an expert committee just for apathy or some lame excuse as they do not have valid reasons to counter the diagnosis made. In the absence of the committee member, substitution must be arranged instead of postponing the meetings indefinitely for decades. This has not been done so far in India. ,,,,,,,,, Not finalizing the diagnosis is an important reason for the high CFR because timely appropriate epidemic management measures are not undertaken. Politicians, administrators and departmental heads should participate in the meetings and should take instantaneous decisions and issue orders to rectify the defects.
An excellent recovery is possible despite an illness that is very acute and life-threatening. Encephalitis results in two types of injury to the brain, namely Primary and Secondary injury. , Primary injury is directly because of the pathogen. It involves a small area and is repaired by the body in most cases because pathogens are not as virulent as was thought before. During the acute phase of AES, due to malfunctioning of protective reflexes, brain and other organs are vulnerable to situations that precipitate hypoxia, hypoglycemia, hypotension, etc. Secondary injury is because of not providing timely supportive care to prevent hypoxia, hypoglycemia and hypotension during this acute phase. It increases with time till supportive care is provided. This is because glucose and oxygen supplies, which are essential to maintain and repair the brain and other organs, are preserved by supportive care. Status epilepticus and fever increase the requirements of glucose and oxygen, and any limitation of their supply aggravates the secondary injury. The pathologic process is frequently temporary or reversible when basic life support is appropriately instituted on time.  On the other hand, deficiency in oxygen or glucose supplies or hypotension result in increased morbidity and mortality. Though neuronal plasticity (ability to form new circuits by neurons) compensates to a great extent, some deficits may persist as sequelae.
Acute encephalitis syndrome treatment comprises of pathogen specific treatment and nonspecific treatment. Specific treatment prevents primary damage (by attacking the pathogen), and nonspecific treatment prevents secondary damage. For ~90% AES cases, there is no specific treatment, and there are no effective antiviral drugs. ,, Therefore, timely nonspecific treatment can and must be given at the earliest to save the brain and other organs from secondary damage. Very few deaths are directly due to the virus, and most are preventable with prompt and early basic supportive care bringing down CFR to <1%. Similar degree of lowering of morbidity is also possible. ,,,,,, Ignorance about the importance of timely basic supportive and symptomatic medical and nursing care for prevention of secondary damage is killing more children than the pathogen per se. , Currently, every case is being referred (without basic support) to the tertiary care center because of lack of facilities or staff for reducing the work load. People also think that better treatment is available in TCH, which is very attractive with its air-conditioned Intensive Care Units (ICUs), sophisticated ventilators and blinking lights. Hence, they travel for many hours in ill-equipped vehicles to go to ICUs.  Lack of oxygen, glucose and development of problems like seizures or raised intracranial tension during the long duration of transportation result in irreversible secondary damage causing disability or even death. This is the commonest cause of disability or death. ,,, Most of the times the brain damage was too severe to be reversible, and TCH are unable to save the patients. , This can be minimized by stabilizing the case before referring to well-equipped district hospitals or TCH if referral is absolutely essential.,.
Hence, to reduce AES deaths, treatment must be started at the earliest. Simple ways to diagnose AES were evolved so that even parents can diagnose and start first aid for AES. , "Treatment facilities must be made available at places where cases occur" and the treatment facilities must be located within 10 km or be reachable within 30 min (as was done in Telangana/Andhra Pradesh States of India). , So, PSCH must be increased and improved. These facilities should be designated as Encephalitis Treatment Centers (ETCs) to impress the public.  After 30 min, brain damage may be too severe to save the patient. Community awareness about these facilities must be created through mass media. In areas where PSCH is located at distances beyond 10 km, Health Sub Centers/Additional Primary Health Centers should be upgraded as ETCs. , Good ambulance services must be provided. Preferential strengthening of PSCH reduces CFR of AES to a greater extent. Preferential improvement of TCH can have disastrous consequences of increasing preventable deaths. For developing and underdeveloped countries with limited finances, improving PSCH is the most practical way to reduce CFR.  In 2011, incidence of AES in Nepal was 2.599 times that of Uttar Pradesh but CFR of Uttar Pradesh was 8.527 times that of Nepal  because Nepal improved rural hospitals, and Uttar Pradesh improved TCH.  In Nepal, PSCH were strengthened with an effective referral mechanism because of the limited financial resources, poor transport system, fewer TCH (ICU), frequent road blocks due to political disturbances and in addition, poverty forced patients to go to the nearest PSCH. Nepal's CFR is reduced to <1% [Figure 2] and [Figure 9]. 
|Figure 9: Case fatality rate in Nepal and Uttar Pradesh. Odds Ratio and z-value are also shown. Modified with permission|
Click here to view
Doctors, nurses, and paramedical staff of public and private sector should be trained on management of AES. Only willing and dedicated staff must be trained and posted at these health facilities in the epidemic prone areas. It must be assured that they will not be transferred for 5 years.  Medical and nursing students help may be taken if necessary.
Nonspecific treatment with a negligible financial burden that improves the prognosis significantly includes measures like laying the patient on one side, keeping the airway patent, maintenance of normothermia, keeping a loop of the intravenous line below the bed level (to prevent air embolism), treating cerebral edema, intracranial hypertension, seizures, not disturbing the patient, oral nutrition at the earliest possible time. Treating the patient in rural hospitals, avoiding unnecessary referral to the TCH, can reduce the CFR almost to zero. 
Bacterial, fungal, parasitic (like cerebral malaria) and some viral encephalitides (like Herpes simplex, Varicella-zoster) have specific drug treatment.
With the expenditure of one TCH bed, we can maintain three PHCs or one SCH for 1 year. 
Epidemic preparedness and rapid response must be improved.
In many states like Assam and Uttar Pradesh, patients are admitted to TCH as the peripheral treatment centers are not properly equipped. In most of the district hospitals, pediatric and adult ICUs are not functional. So even if AES/JE patients are referred without delay, proper intensive management cannot be initiated. The laboratory premises for diagnosis of JE cases are available in most of the district hospitals but equipment, logistics and laboratory consumables, as well as maintenances, are missing. Quality assurance procedures are not in place. There is also a shortage of ICU staff and ICU specialists at the block level in highly endemic districts. There is no formal training of Pediatricians on the management of AES/JE. Training or refreshing training sessions have to be conducted at all levels to improve/standardize case management of AES/JE. There are no facilities for Physical Medicine and Rehabilitation units. So, ICU facilities are to be established in all high-priority districts. 
Where ICUs are functional, proper working of the referral systems, active follow-up, including disability management must be ensured. Patients with complications are referred up, but feed-back referral and follow-up care is missing. Often even the referral to a higher center is thwarted by lack of appropriate secondary services in the district.
Vacant positions (nurses, doctors) need to be filled up on a priority basis. Tasks and responsibilities, including supervisory responsibilities, for all levels of staff need to be clearly identified and communicated to staff to improve performance.
Lack of devotion to work and absenteeism are rampant at all levels.  Not paying travel and dearness allowances to epidemic investigation teams due to various reasons is discouraging most doctors. In addition, not providing protection from infection and attractive monetary benefit to them are other important reasons for efficient investigators not joining the team. Attracting qualified, sincere and hard-working doctors to work in PSCHs is a difficult task. Incentives must be provided to staff willing to work in remote hard-to-reach locations/populations. Creating public confidence in PSCHs through mass media is essential. ,
There are inadequate finances to support the program, and where funds are allocated, there is poor absorption of funds due to problems of flow and utilization. Frequently funds are wasted for buying less important things without fixing priorities. Hundreds of crores have been spent to establish ICUs. Most of them do not function due to either defect in the machinery or lack of qualified staff. Machines for ICUs are purchased on a priority, but staff to maintain them are either not sanctioned or not posted.
Powers and accountability must go together. Appointments should be based on a combination of qualifications, experience, dedication to work and past performance. Regular feed-backs on disease outbreaks and involvement in epidemic response improve systems accountability.
People without adequate health/medical knowledge are being posted as health secretary and health minister.  They can at least take help from committees of experts of various diseases to solve this issue.
Multiple ministries have to coordinate their work if CFR has to be brought down. Intersectoral collaboration between Ministry of Health and Family Welfare, Ministry of Drinking Water Supply and Sanitation, Ministry of Women and Child Development, Ministry of Social Justice and Empowerment, Ministry of Rural Development, Ministry of Urban Development and Roads and Buildings is essential. 
The best way to reduce CFR of encephalitis in developing and underdeveloped countries is to increase and improve PSCH and sensitize politicians, administrators, medical/nursing professionals and more importantly to impress and convince the public to utilize them. Inadequate health education is the root cause of poor environmental sanitation and delay in seeking timely treatment.
Involvement of private sector in training sessions and in reporting AES according to NVBDCP guidelines and standard operating procedures is essential. Public-Private Partnerships are to be encouraged to engage the private sector in its contribution to public health goals. There is a need for integrated information and services across private and public sector so that diseases seen in the private nursing homes also get the follow-up care and trigger public health action.
| Conclusions and Projections|| |
Let us not accept defeat without fighting AES. Vaccination, environmental sanitation, vector control, health education and attention to prompt diagnosis and treatment in rural hospitals are the four essential pillars for reducing CFR of AES. Red tapism, nepotism, corruption and egoism are the often untold major reasons for poor performance at all levels. Until these are rectified, encephalitis continues to claim precious lives. Though we all know that everything follows the bell curve, the burning question is whether we are at its peak or still not reached the peak!
| Acknowledgments|| |
I would like to offer my special thanks to Indian Public Health Association for inviting me to deliver Dr. B.C. Das Gupta oration, 2014. My sincere thanks are to PATH, WHO, WHO-SEAR, WHO-IPD, NVBDCP, GAVI (Global Alliance for Vaccines and Immunization), Environmental Health Project (EHP) for BBIN (Bhutan, Bangladesh, India and Nepal) countries, Government of India, Government of Andhra Pradesh and various other states, Child Health Division, Department of Health Services, Ministry of Health and Population, Teku, Kathmandu, Government of Nepal.
I am particularly grateful for the encouragement given by Dr.Julie Jacobson, Finance Director, Bill and Melinda Gates Foundation, Seattle, USA which made me spread the facts of the real reason for the high CFR of encephalitis. I also thank tens of thousands of doctors, nurses and paramedical workers of India and Nepal, who worked with me and struggled to achieve this goal. Finally, I wish to acknowledge the help of the reviewers and the publisher for their valuable suggestions to make this article better.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]