Introduction
Japanese encephalitis (JE) is a mosquito-borne flaviviral zoonosis that causes encephalitis in people in the Asia-Pacific region (Wang & Liang, 2015). It is estimated that >1 billion people live in areas suitable for local JE virus (JEV) transmission (Moore, 2021) and annually, JEV has been estimated to cause 68,000 human cases, including 13,600-20,400 deaths, with estimated 51,000 (75%) cases occurring in children ≤14 years old (Campbell et al., 2011). Although most JEV infections are mild (fever and headache) or asymptomatic, approximately 1 in 250 infections results in severe clinical illness (Amicizia, Zangrillo, Lai, Iovine, & Panatto, 2018). The case fatality rate can reach 30%, and of those who survive, 30% suffer permanent neurological sequelae including ‘locked-in syndrome’ (World Health Organization, 2019).
Japanese encephalitis virus is a multi-host pathogen and reservoir species include ardeid birds and pigs, with mosquitoes (primarilyCulex sp.) as biological vectors (Wang & Liang, 2015). People are incidental, non-competent hosts, also becoming infected via the bite of Culex species mosquitoes. There is no specific antiviral treatment for patients affected with JEV; therefore, supportive medication is given to relieve symptoms and stabilize the patient. In India, the incidence and case fatality rate of acute encephalitis syndrome (AES) – in which JE is identified in 5-20% of AES cases – has fallen since 1978 through implementation of JE vaccination campaigns, improved surveillance, and more rapid treatment at designated Encephalitis Treatment Centres (Srivastava, Deval, Mittal, Kant, & Bondre, 2021).
Japanese encephalitis has been recognised in several tropical and subtropical states of India, and recent JEV spread in the northern temperate states of India has been reported (Mote et al., 2023). In eastern Uttar Pradesh (UP) state (Kumari & Joshi, 2012; A. K. Singh et al., 2020; G. Singh et al., 2013), extensive and recurrent outbreaks are reported, and together with the state of Assam, contribute the greatest proportion of the total JE burden in India; from 2015-2021, 11,326 human JE cases were reported from 23 states in India, with 2265 and 3334 cases (49% overall) from the states of Assam and Uttar Pradesh, respectively (Directorate of National Vector Borne Disease Control Programme, 2022).
Multiple landscape factors including topography, waterlogged rice-paddy fields, piggeries without mosquito control, pig-keeping in residential areas, high pig populations, and the prolonged rainy season support the breeding of Culex mosquitoes and perpetuate the transmission of JEV to pigs people in these two states (Khan et al., 1996; Kumari & Joshi, 2012; Murhekar, Vivian Thangaraj, Mittal, & Gupta, 2018). Rainfall has been demonstrated to be strongly associated with JEV outbreaks in India (Borah, Dutta, Khan, & Mahanta, 2013; H. Singh, Singh, & Mall, 2020), and recent analysis of India-wide JEV incidence in people indicated that outbreak risk was strongly associated with the habitat suitability of ardeid birds, both pig and chicken densities, and the shared landscapes between fragmented rain-fed agriculture and both river and freshwater marsh wetlands (Walsh et al., 2022).
In endemic regions, JEV can circulate in pig populations because their high birth rate provides a continuous supply of susceptible pigs and their viraemia levels are sufficient to infect mosquitoes for 3-5 days – hence they are known as amplifying hosts (Ladreyt, Durand, Dussart, & Chevalier, 2019). In Asia, pigs are preferentially fed on by the main mosquito vector of JEV between pigs and people, Culex tritaeniorhynchus , and pigs have been shown to seroconvert 2-3 weeks before JEV infection is detected in humans (Borah et al., 2013; Cappelle et al., 2016; G. Singh et al., 2013; Van den Hurk, Ritchie, & Mackenzie, 2009). Sero-surveillance of pig populations can therefore be an important component of JEV surveillance to estimate the risk of zoonotic transmission and guide prevention strategies including mosquito control, bite prevention, and human or pig vaccination programs (Duong et al., 2011; Kumar et al., 2020; Ruget et al., 2018). Despite this, few JEV studies have investigated the use of sero-surveillance of JEV in pigs. In a study of IgG and IgM seroprevalence for JEV in 488 pigs in endemic regions in India (Kolhe et al., 2015), IgG ranged from 20% in Uttar Pradesh to 35.2% in Northeast India. In contrast, IgM seroprevalence in the same samples was highest in Goa (39%) and lowest in Northeast India (22.7%) and Uttar Pradesh (20%). Overall, higher seroprevalence of IgM was detected, possibly because the study was conducted in June to October when increased transmission of JEV occurs and pigs were recently infected. In an earlier study of IgG seroprevalence in 500 pigs from April 2013 – May 2014, seroprevalence was 61.5% in Tripura, 29.3% in Uttar Pradesh, and 28.7% in Punjab, with highest overall seroprevalence between July and October (H. Dhanze et al., 2014). Whilst these studies give some insight about JEV epidemiology in pigs – for example, the relative seroprevalence in pigs between regions and months – there is limited detail about trend, associations with climate or landscape variables, and differences between IgG and IgM antibodies.
The objective of this study was to describe the spatio-temporal distribution of JEV seroprevalence in the pig population of eastern Uttar Pradesh, India between 2013 and 2022, and investigate seasonality, trend, and associations between seroprevalence and climate variables (rainfall, temperature, and humidity) in the region. The aim of this study was to provide insights about the epidemiology of JEV in pigs in the region over a longer period than has previously been conducted and assess how sero-surveillance of JEV in pigs could be most useful to inform disease control programs to prevent JEV impact in people.