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.