Japanese encephalitis: Strategies for prevention and control in India

Ruchir Rustagi; Saurav Basu; Suneela Garg

doi:10.4103/INJMS.INJMS_22_18

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Year : 2019 | Volume : 10 | Issue : 1 | Page : 12-17

Japanese encephalitis: Strategies for prevention and control in India

Ruchir Rustagi, Saurav Basu, Suneela Garg
Department of Community Medicine, Maulana Azad Medical College, New Delhi, India

Date of Submission	07-Nov-2018
Date of Acceptance	04-Jan-2019
Date of Web Publication	18-Feb-2019

Correspondence Address:
Dr. Ruchir Rustagi
Department of Community Medicine, Maulana Azad Medical College, New Delhi
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/INJMS.INJMS_22_18

Abstract

Japanese Encephalitis (JE) is an important re-emerging vector-borne zoonotic disease of the 21^st century which is the most important cause of morbidity and mortality due to pediatric viral encephalitis in Asian populations. India and China together report 95% of the disease burden where it is also an important cause of acute encephalitis syndrome. JE is a neglected tropical disease which disproportionately afflicts poor and economically disadvantaged populations in rural regions of low and middle-income countries which often lack well-equipped tertiary care centers for the management of JE cases presenting with central nervous system manifestations and related complications. JE has large animal reservoirs among pigs and water birds which renders JE elimination difficult. Hence, current strategy for JE prevention and control pursues a combined approach inclusive of expansion of JE vaccination coverage in endemic regions, vector control, and surveillance. Unfortunately, the lack of public health infrastructure, economic resources, and lack of political commitment has resulted in most endemic countries in the developing world failing to take adequate steps for achieving these recommended measures for JE control, especially with regard to developing surveillance capacities and reference laboratories for the diagnosis of JE. Moreover, the threat of JE has increased in recent years due to factors such as climate change and lack of economic development in several endemic zones even as the disease has begun affecting adult populations. Evidence from surveillance data in some countries also suggests that increase in vaccination coverage for JE does not necessarily correlate with decline in JE disease burden. Ultimately, JE is likely to persist as a major public health problem in the developing world and impede their economic development unless it receives adequate attention from the global health community.

Keywords: Control, encephalitis, India, prevention

How to cite this article:
Rustagi R, Basu S, Garg S. Japanese encephalitis: Strategies for prevention and control in India. Indian J Med Spec 2019;10:12-7

How to cite this URL:
Rustagi R, Basu S, Garg S. Japanese encephalitis: Strategies for prevention and control in India. Indian J Med Spec [serial online] 2019 [cited 2023 Jun 9];10:12-7. Available from: http://www.ijms.in/text.asp?2019/10/1/12/252471

Introduction

Zoonotic diseases or zoonoses are the most frequent and dreaded risk to humankind. They occur throughout the world, across the national boundaries, hence needing global surveillance and response for their effective containment and control. Zoonotic diseases are a major public health problem in India. Japanese encephalitis (JE) is an emerging zoonotic disease in India causing several outbreaks, thus leading to considerable morbidity and mortality in the recent past.

JE is a vector (mosquito) borne viral zoonotic disease, caused by an arbovirus (flavivirus) belonging to family Flaviviridae. The viral agent has five genotypes which mainly affect the central nervous system.^[1] The World Health Organization (WHO) has attributed JE to be the most important cause of mosquito borne viral encephalitis in endemic Asian countries especially in the pediatric age group (0–14 years), where 75% of the cases occur. An estimated 67,900 cases of JE are reported annually, with approximately 13,600–20,400 deaths, while 2 billion people are at risk located in 24 WHO member countries. Out of these estimated numbers of incidence, only 10% are reported to the WHO. India and China experience 95% of the reported disease burden of JE. Two-thirds of the at-risk population for JE is in China and India only.^[2] Most of the cases of JE in humans are incidental. Majority of cases are asymptomatic or subclinical. Cases with clinical manifestations present with features of encephalitis, and are at risk of development of seizures, impaired consciousness, coma, and other neurological deficits. There is a risk of death due to the high case fatality rate (20%–40%) of the disease in the absence of availability of any specific treatment.^[1] In endemic regions, the disease is usually confined to the pediatric age group especially below 15 years since immunity is acquired by adulthood from subclinical infections. However, JE is a disease of all age groups and may affect adults particularly when the disease gets introduced into nonendemic areas or in regions which lack significant childhood immunization coverage against JE virus (JEV).^[3],[4]

JE is also an important re-emerging disease of the 21^st century as evident from outbreaks reported after hiatus of decades in some Asian countries or regions where it was unreported for decades.^[5],[6],[7] Furthermore, it is a disease with considerable epidemic potential even in nonendemic regions which harbor and provide conducive environments for JE reservoir hosts and vectors. In this article, we review the current strategy for prevention and control of JE and explore the global challenges in combating the disease.

Epidemiology of Japanese Encephalitis

The natural reservoir of infection of JEV includes animals such as pigs, and birds such as pond herons, cattle egrets, poultry birds and ducks. The role of bovines and bats in the transmission of JE has been found to be doubtful. Mosquitoes from the Culex vishnui group consisting of species namely, Culex tritaeniorhynchus, C. vishnui, and Culex pseudovishnui become infected with the virus while feeding upon viraemic hosts and acquire capability to transmit infection. Many other species of mosquitoes have been found to be positive for JE from time to time.^[1] Culex mosquitoes may transmit the infection to man, who is a dead-end host due to very low viremia levels, thus preventing further transmission and infection of new mosquitoes.^[8],[9] Culex mosquitoes may feed upon cows, horses and men (incidental or dead end hosts) and pigs (amplifying hosts) which permits circulation of the JEV in an enzootic cycle.^[8],[9] Amplifying hosts can maintain JE outbreaks for several weeks.

The risk factors for transmission of JE are:^[1],[10]

Living in proximity to rice fields as Culicine mosquitoes breed in abundance in paddy fields. A study by Raju et al. found a correlation between adult density of Culex tritaeniorhynchus and heading stage of the paddy crop^[11]
Living with pigs (amplifier hosts) in the peri-domestic environment is a risk factor for transmission. In urban areas, rearing of pigs especially around slums along with breeding of culex mosquitoes can facilitate transmission of JE^[12]
Lack of immunization against JE, especially in the pediatric age groups in endemic regions
Males are affected more than females
In temperate regions, the risk of JE outbreaks increases during late summers in the rainy season probably due to greater breeding of the Culex mosquito vector.^[13] However, the JEV may keep replicating in certain animals (exclusive of mosquitoes) which implies its ability to settle during winter months.^[14]

Clinical Disease and Management

Majority of cases infected with JEV are asymptomatic, with only around 1 in 300 human cases of JE manifesting clinical symptoms.^[1] The incubation period in humans, following mosquito bite varies from 5 to 15 days. Majority of the cases with clinical manifestations present with mild fever and headache. JE patients with a history of acute onset of fever may progress to altered sensorium which may be accompanied by convulsions. Focal neurological deficit may subsequently be present which can be stationary or progressive.^[1] The diagnosis of JE via serological testing of JEV-specific IgM antibody in cerebrospinal fluid and serum is recommended method for laboratory diagnosis but specificity can be low due to cross reactivity.^[15] No specific antiviral treatment is available against the disease, and the mainstay of management remains supportive therapy only.^[1]

Current Strategies for the Prevention and Control of Japanese Encephalitis

Vaccination

Effective vaccines for JE are available and universal vaccination coverage in endemic regions is the most important mechanism/strategy for preventing JE outbreaks. In contrast to developed nations like Japan, where even animals susceptible to JE have been vaccinated for over five decades, several developing nations with large populations at risk of JE like Bangladesh began campaign for vaccination against the disease only in the 21^st century. The introduction of JE immunization in endemic regions can significantly reduce the incidence of JE and acute encephalitis syndrome (AES) case burden in those areas.^[16]

Vaccines against JE belong to four types of classes, which are all based on Genotype 3 strains. These include inactivated mouse brain-derived vaccines, inactivated Vero cell-derived vaccines, live attenuated vaccines, and live recombinant (chimeric) vaccines [Table 1].^[17] JE vaccines have been reported to have a good safety profile and there are no listed absolute contraindications. In immunocompromised patients, inactivated JE vaccine is recommended. JE vaccination should be provided to health-care workers (HCWs) and those traveling to endemic regions during transmission season.

Table 1: Vaccination in Japanese Encephalitis *(Adapted from World Health Organization position paper)

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The WHO has considered JE immunization to be the most important evidence-based guideline for reducing burden of the disease in endemic regions and thus, recommended the inclusion of JE vaccination in national immunization programs.^[17] Mass vaccination strategy of vulnerable populations has also been recommended.^[7]

There exist some fundamental barriers to attaining universal JE vaccination coverage, which include the following:

In most of the developing nations, routine immunization coverage tends to be low, which renders large sections of the at-risk populations defenseless against the threat of JE
Moreover, Immunization coverage in the developing world is lower in rural areas compared to the urban areas and the national average. Unfortunately, JE is predominantly a rural disease which increases the vulnerability of the population at-risk
Herd immunity to JE is absent in humans, since we are a dead-end host so the disease, cannot be transmitted from one individual to another. This implies the necessity of a high vaccination coverage required to control the disease. Due to the presence of animal reservoirs, vaccination of animals becomes necessary for eliminating the disease. This is however, not economically sustainable for most developing nations where JE exists as a public health problem
The WHO recommends provision of JE vaccination by governments even in those areas where reporting of JE confirmed cases is low but the potential for outbreak exists due to availability of suitable environmental conditions favoring JEV transmission. However, policy makers may be reluctant to advance JE vaccination in low burden regions due to the excess costs involved. It is imperative for governments/policy makers to consider the expansion of vaccination coverage in districts adjoining the high-risk endemic zones for prevention of outbreaks^[18]
Mass vaccination approaches in adults which have been introduced in certain endemic JE regions may not be cost effective since majority of adults in these areas have developed immunity to JE due to subclinical infection or clinical infection during childhood^[19]
Multiple doses are required for attaining immunity among all available JE vaccines
Vaccination of pigs for controlling JE is rendered ineffective by the high turnover of pig population and the decreased efficacy of vaccines in piglets due to maternal antibodies.^[20]

Effective vector control measures, keeping in view the resistance profiling

Reduction of breeding sources of larvae: Since Culex mosquitoes breed predominantly in paddy fields, the employment of effective water management system and the use of biofertilizer have been recommended for reducing the mosquito breeding^[1]
Use of composite fish culture and larvivorous fish to curb the larvae at the breeding sites
Use of novel bio-larvicides.^[21]

Personal prophylaxis measures like use of pyrethroid treated bed nets or insecticide impregnated nets can be used in JE control. Indoor residual spray, fogging and antilarval measures are ineffective in JE control.^[1] Ultra-low volume fogging with malathion is effective against JE vectors.^[22]

Surveillance

JE surveillance is a part of AES surveillance involving syndromic (clinical) surveillance, vector (entomological) surveillance and sero-surveillance (veterinary-based surveillance).^[1],[23] Surveillance activity in endemic regions is recommended throughout the year and rendered part of integrated disease surveillance activity. Good quality JE surveillance is essential for the detection of early warning signals of impending JE outbreaks which include increase in cases and clustering which is higher than expected for the region and seasonality, detection of viral activity in vectors and animal (zoonotic) reservoirs.^[22] Furthermore, surveillance data is useful in assessing the impact of vaccination and vaccine efficacy for JE prevention and control.^[23]

The WHO recommends the inclusion of a standard case definition for JE/AES and classification of cases into suspected (clinical correlation), probable (presumptive laboratory results) and confirmed (confirmatory laboratory results). Based on WHO Criteria, surveillance activity should be carried out simultaneously nationwide throughout the year in both endemic and nonendemic regions (where disease has been reported but vector is absent).^[24] However, in developing nations including India, sentinel surveillance in all hospitals in endemic regions is used as a reasonable alternative to the more resource intensive regular, nationwide surveillance.^[23] Globally, by 2012, 18 of the 24 countries with JEV transmission risk had any established mechanism of JE surveillance.^[25] Wang and Liang have classified JE-endemic countries into four levels based on their surveillance strategies and immunization coverage strategies [Table 2].^[26]

Table 2: Surveillance and Immunization Status in Nations with reported Japanese Encephalitis (Adapted from Wang and Liang)

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There exist several challenges in ensuring sustenance of good quality JE surveillance activities in endemic and developing areas. Sentinel surveillance sites may often lack laboratory facilities for JE diagnosis which undermines the quality of surveillance. Furthermore, studies have suggested that existing JE Serology (IgM-MAC-ELISA) may underestimate recent infection with JEV in comparison to real-time reverse transcriptase polymerase chain reaction leading to spuriously low estimation of JE incidence.^[27] Monitoring of virus mutation in vectors (mosquitoes), seroconversion rates in amplifying vectors like pigs and water birds, nationwide and the viral antibodies circulating among human populations in endemic regions are also essential for generation of Early Warning Signals for the rapid detection of JE outbreaks by surveillance systems.^[22],[23] Hence, the strengthening of laboratory facilities for serodiagnosis is a critical objective for strengthening of JE surveillance.^[23] Since cases of non-JE AES are more common in India, laboratory facilities should also be equipped to detect multiple etiological pathogens.

Behavior change communication

The effective use of behavior change communication (BCC) has been employed with considerable success in controlling other vector borne diseases like malaria.^[28] It can be expected that BCC can also play an effective role in improving JE vaccination coverage and also the promotion of the use of personal prophylaxis measures to protect against mosquito bites like covering the whole body by wearing full length clothes, application of mosquito repellents and using bed nets especially during post monsoon seasons, reduce human contact with animal reservoirs like pigs especially during dusk to dawn which is the peak biting period of mosquitoes.

Upgradation of health-care facilities and training of health-care workers

Health-care facilities at endemic JE regions should have round-the-clock emergency services with trained HCWs and necessary equipment for management of unconscious patients, reduction of increased intracranial pressure, treatment of convulsions and managing respiratory failure. Pediatric intensive care units with sufficient capacity during outbreak seasons are particularly required in endemic regions. Neurological rehabilitation of JE affected patients should also be available for disability limitation.^[22]

HCWs in endemic facilities also require to be trained and sensitized while dealing with JE cases. A cross-sectional study conducted in a district in the state of Assam in India by Ahmad et al. (2015) found poor knowledge in HCWs involved in the management of clinical JE cases although they had good knowledge of the epidemiological characteristics of the disease and its prevention.^[29]

Intersectoral coordination for provision of safe drinking water, housing, nutritional status, and sanitation in endemic regions in order to reduce overall AES burden is an important strategic element incorporated in the Indian national program for control of JE.^[22] Nevertheless, efforts in these directions require long-term commitment with enduring political will.

Case Study: Japanese Encephalitis in India

JE is one of the most important causes of AES in India with considerable prevalence in many districts. The government of India identified 104 endemic districts in 11 states of India based on comprehensive epidemiological data and introduced a phased JE mass vaccination program using the live attenuated JE vaccine between 2006–2011 in the 1 to 15-year-old population.^[30] JE vaccine was also integrated with the Universal Immunization Program for vaccinating cohorts from 9 months of age in these states. However, despite the expansion in JE vaccination coverage, the reported number of AES including JE cases and attributable deaths have increased between 2009 and 2014 [Figure 1].^[31] This suggests that the complex underlying dynamics of disease transmission in JE requires further exploration in order to discover ways of controlling JE in populations reporting enhanced vaccination coverage.

Figure 1: Acute encephalitis syndrome and Japanese encephalitis situation in India before and after expansion of Japanese encephalitis vaccination coverage

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Conclusion

JE is a significant public health problem which affects mostly poor, vulnerable populations in rural areas with limited health-care resources and endemic zones with low vaccination coverage. Improved standards of living, urbanization and increased JE vaccination coverage have considerably reduced JE burden in some countries like China while in some others like India, the result has been mixed.^[26] New challenges in JE have emerged in recent years as evidenced by increase in JE outbreaks among adult populations in India.^[3],[4] Low income countries in Asia experiencing high population growth, increased rice cultivation and pig rearing to feed their populations are particularly at risk of JE outbreaks.^[20],[32] Paddy cultivation areas in JE endemic regions in the developing world are required to meet primary nutrition requirements for their growing populations. Climate change resulting in extended rainfall and warmer temperatures can also tend to increase JE outbreaks in endemic regions by promoting environments conducive to breeding of the vector (Culex) mosquitoes. Efforts to control JE need to be reoriented toward countering these new challenges.

Unfortunately, JE control programs have greater likelihood of inadequate resource allocation due to high burden of other zoonosis like Rabies which share similar geographical burden as in the Indian context. The development of low cost, safe and efficacious vaccines with ideally single dosing for providing lifetime protection and which serves both man and animal remains an enduring need for JE control.^[33] The enhancement of laboratory diagnostics facilities and development of reference laboratories for improving surveillance also requires greater attention in the goal towards elimination of JE as a public health problem. Ultimately, weaning away local populations from pig rearing in JE endemic areas requires provision of alternative means of livelihood to vulnerable populations and overall economic development of the regions.

Financial support and sponsorship

None.

Conflicts of interest

There are no conflicts of interest.

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Figures

[Figure 1]

Tables

[Table 1], [Table 2]

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