Japanese Encephalitis and Associated Environmental Risk Factors in Eastern Uttar Pradesh: A time series analysis from 2001 to 2016.

India and other Southeast Asian countries are severely affected by Japanese encephalitis (JE), one of the deadliest vector-borne disease threat to human health. Several epidemiological observations suggest climate variables play a role in providing a favorable environment for mosquito development and virus transmission. In this study, generalized additive models were used to determine the association of JE admissions and mortality with climate variables in Gorakhpur district, India, from 2001-2016. The model predicted that every 1 unit increase in mean (Tmean;°C), and minimum (Tmin;°C) temperature, rainfall (RF; mm) and relative humidity (RH; %) would on average increase the JE admissions by 22.23 %, 17.83 %, 0.66 %, and 5.22 % respectively and JE mortality by 13.27 %, 11.77 %, 0.94 %, and 3.27 % respectively Conversely, every unit decrease in solar radiation (Srad; MJ/m/day) and wind speed (WS; Kmph) caused an increase in JE admission by 17% and 11.42% and in JE mortality by 9.37% and 4.88% respectively suggesting a protective effect at higher levels. The seasonal analysis shows that temperature was significantly associated with JE in pre-monsoon and post-monsoon while RF, RH, Srad, and WS are associated with the monsoon. Effect modification due to age and gender showed an equal risk for both genders and increased risk for adults above 15 years of age, however, males and age groups under 15 years outnumbered females and adults. Sensitivity analysis results to explore lag effects in climate variables showed that climate variables show the strongest association at lag 1 to 1.5 months with significant lag effect up tp lag 0-60 days. The exposure-response curve for climate variables showed a more or less linear relationship, with an increase in JE admissions and mortality after a certain threshold and decrease were reported at extreme levels of exposure. The study concludes that climate variables could influence the JE vector development and multiplication and parasite maturation and transmission in the Gorakhpur region whose indirect impact was noted for JE admission and mortality. In response to the changing climate, public health interventions, public awareness, and early warning systems would play an unprecedented role to compensate for future risk.