Vaccination is the mainstay of prevention strategies for Japanese encephalitis – the child killer disease that recently caused many deaths in Gorakhpur, Uttar Pradesh. In this article, Dr Kaushik Bharati discusses why the vaccine drive in India has failed to reach its full potential in the fight against the disease, and what can be done about it.

Japanese encephalitis (JE) has been in the headlines recently due to the deaths of a large number of children at B.R.D. Medical College in Gorakhpur, Uttar Pradesh (UP). JE, also known as ‘brain fever’, is caused by the JE virus (JEV), which belongs to the same family (Flaviviridae) as yellow fever virus, dengue virus, and Zika virus. It is spread by the bite of infected Culex mosquitoes, primarily Culex tritaeniorynchus. The virus normally resides in natural reservoirs like pigs and wading birds and therefore, the disease cannot be totally eradicated. JE is the most important viral encephalitides in Asia and is responsible for high mortality and morbidity. Children below 15 years are especially at risk. There is no specific antiviral drug for the treatment of JE, and vaccination remains the mainstay of prevention strategies (Vrati and Bharati 2016).

Japanese encephalitis outbreaks in Uttar Pradesh

JE is not new in Gorakhpur, or for that matter, in UP. It has been there since 1978, when the first major outbreak occurred in the state, during which 3,550 cases and 1,117 deaths were reported from 40 districts. After the 1978 outbreak, extensive and recurrent outbreaks have been reported from the eastern parts of the state. During the first decade (1978-1987), a total of 9,299 cases and 3,103 deaths attributed to JE were reported from 46 districts. In the second decade (1988-1997), the total number of reported cases and deaths were 10,064 and 3,194, respectively, from 25 districts. During 1998-2009, there were much higher numbers than the preceding decades, with 18,760 JE cases and 4,189 deaths reported from 40 districts in the state. This sharp rise occurred from 1998, and in 2005, a major JE outbreak occurred in UP, mostly confined to Gorakhpur, during which 6,061 cases and 1,501 deaths were reported (Kumari and Joshi 2012). This JE outbreak surpassed all other JE outbreaks in the country.

In recent years (2010-2016), the number of laboratory-confirmed JE cases has hovered between 139 and 410, and the corresponding number of deaths was between 23 and 73. The data for 2017 are provisional (until 20 August 2017; National Vector Borne Disease Control Programme), hence excluded from this analysis. However, these figures could be a gross underestimation, since there was a huge number of Acute Encephalitis Syndrome (AES) cases/deaths during these years, which could plausibly also include many more JE cases/deaths that remained unconfirmed.

Currently available JE vaccines in India

Currently, there are three vaccines available in India. Two are manufactured by Indian companies, while another is imported from China and is exclusively used in the Universal Immunization Programme (UIP) of the Government of India. These vaccines are briefly described below:

• JENVAC®: This vaccine is manufactured by Bharat Biotech International Ltd., a Hyderabad-based company. It is an inactivated (killed) Vero-cell derived vaccine prepared from an Indian strain of JEV. Data from a two-dose study showed that a single dose of the vaccine was sufficient to elicit the immune response as the subjects who received a single dose were 98.67% seroprotected (Bharat Biotech). It is priced at Rs. 990 per piece (Indiamart).
• JEEV®: This vaccine is manufactured by Biological E Ltd., based in Hyderabad. It is a purified inactivated (killed) vaccine that uses the SA 14-14-2 strain of JEV. It is a two-dose vaccine and the primary immunisation is given four weeks apart (Biological E). It is priced at Rs. 985 per piece (Indiamart).
• SA 14-14-2: This vaccine is manufactured by the Chengdu Institute of Biological Products, China. It is a live-attenuated vaccine that is manufactured as per the World Health Organization (WHO) guidelines for production of live JE vaccines for human use. This is a single-dose vaccine that has been licensed for use in China since 1988. Till date, over 400 million doses have been administered in China and other Asian countries, with a brilliant safety record. Recently the SA 14-14-2 vaccine has been licensed for use in India, Nepal, Sri Lanka, Thailand, and South Korea. In India, the imported SA 14-14-2 vaccine has been used to immunise over 9.3 million children (aged between 1 and 15 years) in the summer of 2006 in four JE-endemic states (Assam, West Bengal, Bihar, and Jharkhand), besides UP. A major advantage of this vaccine is that it is inexpensive (Rs. 10 per dose; information obtained through personal communication) and hence is ideal for mass vaccination campaigns (Bharati and Vrati 2009).

What are the causes of vaccine failure?

The Government of India has made vaccination against JE part of the routine immunisation under the UIP in 206 JE-endemic districts in the country (Ministry of Health and Family Welfare, 2015). In spite of this, the JE vaccine has failed to reach its full potential. The major causes of vaccine failure are briefly discussed below:

• Low vaccine coverage: In spite of vaccine immunisation efforts, vaccine coverage is low. A recent ICMR (Indian Council of Medical Research) study (Murhekar et al. 2017), which included 840 children (210 from each of four districts in UP) indicated that the JE vaccine coverage for two doses in Gorakhpur division was only 42.3%. Thus, although three of four children aged 25-36 months in Gorakhpur division received the first dose the coverage for the second dose was significantly lower. The major reason for this is that the vaccinators were not aware that the second dose of JE vaccine could be given simultaneously with other UIP vaccines like measles and DPT (diphtheria, pertussis, tetanus).
• Poverty: Since many of the patients come from the economically weaker section of the society, often leading a hand-to-mouth existence, taking a child for vaccination would mean losing a day’s wages. Hence, this can have an indirect impact on a vaccination campaign.
• Malnutrition: Malnutrition goes hand-in-hand with poverty. Malnourished, poor children therefore are likely to have a much weaker immune system than their healthy counterparts. This translates into a weaker immune response and thereby reduced protection against the pathogen.
• Lack of health awareness: Lack of health awareness is a major factor behind vaccination failure. Moreover, illiteracy can encourage rumour-mongering that can have devastating effects on vaccination campaigns. For example, rumours among the uneducated that a vaccine could cause disease or lead to sterility, could severely cripple a vaccination drive. Of importance is the fact that since vaccination campaigns occurs during periods when epidemics do not occur, most people fail to understand why they need a vaccine – which they perceive as an injection for treating a disease – while they are healthy and disease-free.