Estimates of Japanese Encephalitis mortality and morbidity: A systematic review and modeling analysis

• Published in: PLoS neglected tropical diseases 2022-05, Vol.16 (5), p.e0010361-e0010361
• Main Authors: Cheng, Yuwei, Tran Minh, Nhat, Tran Minh, Quan, Khandelwal, Shreya, Clapham, Hannah E
• Format: Article
• Language: English
• Subjects: Age; Biology and Life Sciences; Care and treatment; China; Countries; Diseases; Encephalitis; Encephalitis, Japanese - epidemiology; Encephalitis, Japanese - prevention & control; Epidemics; Estimates; Estimation; Fatalities; GDP; Gross Domestic Product; Growth rate; Humans; Immunization; Japanese encephalitis; Japanese Encephalitis Vaccines; Medicine and Health Sciences; Morbidity; Mortality; Neurological complications; Patient outcomes; People and Places; Per capita; Philippines - epidemiology; Population density; Population dynamics; Population growth; Prediction models; Regression analysis; Research and Analysis Methods; Risk; Rural areas; Rural populations; Surveillance; Surveillance systems; Survival; Systematic review; Thailand; Tropical diseases; Vaccination; Vaccines; Variables; Vector-borne diseases
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0010361

Japanese Encephalitis (JE) is known for its high case fatality ratio (CFR) and long-term neurological sequelae. Over the years, efforts in JE treatment and control might change the JE fatality risk. However, previous estimates were from 10 years ago, using data from cases in the 10 years before this. Estimating JE disease severity is challenging because data come from countries with different JE surveillance systems, diagnostic methods, and study designs. Without precise and timely JE disease severity estimates, there is continued uncertainty about the JE disease burden and the effect of JE vaccination. We performed a systematic review to collate age-stratified JE fatality and morbidity data. We used a stepwise model selection with BIC as the selection criteria to identify JE CFR drivers. We used stacked regression, to predict country-specific JE CFR from 1961 to 2030. JE morbidity estimates were grouped from similar study designs to estimate the proportion of JE survivors with long-term neurological sequelae. We included 82 and 50 peer-reviewed journal articles published as of March 06 2021 for JE fatality and morbidity with 22 articles in both analyses. Results suggested overall JE CFR estimates of 26% (95% CI 22, 30) in 1961-1979, 20% (95% CI 17, 24) in 1980-1999, 14% (95% CI 11, 17) in 2000-2018, and 14% (95% CI 11, 17) in 2019-2030. Holding other variables constant, we found that JE fatality risk decreased over time (OR: 0.965; 95% CI: 0.947-0.983). Younger JE cases had a slightly higher JE fatality risk (OR: 1.012; 95% CI: 1.003-1.021). The odds of JE fatality in countries with JE vaccination is 0.802 (90% CI: 0.653-0.994; 95% CI: 0.62-1.033) times lower than the odds in countries without JE vaccination. Ten percentage increase in the percentage of rural population to the total population was associated with 15.35% (95% CI: 7.71, 22.57) decrease in JE fatality odds. Ten percentage increase in population growth rate is associated with 3.71% (90% CI: 0.23, 7.18; 95% CI: -0.4, 8.15) increase in JE fatality odds. Adjusting for the effect of year, rural population percent, age of JE cases, and population growth rate, we estimated that there was a higher odds of JE fatality in India compared to China. (OR: 5.46, 95% CI: 3.61-8.31). Using the prediction model we found that, in 2000-2018, Brunei, Pakistan, and Timor-Leste were predicted to have the highest JE CFR of 20%. Bangladesh, Guam, Pakistan, Philippines, and Vietnam had projected JE CFR over 20% for a