Cost of Acute and Sequelae Care for Japanese Encephalitis Patients, Bangladesh, 2011-2021.

Japanese encephalitis (JE) is associated with an immense social and economic burden. Published cost-of-illness data come primarily from decades-old studies. To determine the cost of care for patients with acute JE and initial and long-term sequelae from the societal perspective, we recruited patients with laboratory-confirmed JE from the past 10 years of JE surveillance in Bangladesh and categorized them as acute care, initial sequalae, and long-term sequelae patients. Among 157 patients, we categorized 55 as acute, 65 as initial sequelae (53 as both categories), and 90 as long-term sequelae. The average (median) societal cost of an acute JE episode was US $929 ($909), of initial sequelae US $75 ($33), and of long-term sequelae US $47 ($14). Most families perceived the effect of JE on their well-being to be extreme and had sustained debt for JE expenses. Our data about the high cost of JE can be used by decision makers in Bangladesh.

Cost-effectiveness analysis of Japanese Encephalitis (JE) vaccination program in Bali Province, Indonesia.

OBJECTIVE: The incidence of Japanese Encephalitis (JE) in Bali Province remains high, and is one among the highest in Indonesia. The Indonesian Government initiated the JE vaccination campaign followed by a JE vaccine introduction program in Bali Province in 2018. The JE vaccination program then has been fully integrated into the provincial routine immunization program since 2019. We conducted a retrospective economic analysis of JE vaccination program in Bali Province, Indonesia; considering multiple vaccination strategies. METHODS: We conducted a cost-effectiveness analysis using a decision analytic model comparing two vaccination strategies with no vaccination from the societal and government perspectives. These vaccination strategies were: (1) JE vaccination campaign and introduction program, and (2) a routine JE vaccination program. We compared costs and outcomes for three hypothetical cohorts of 100,000 children followed from birth to the age of 10 years, with impacts measured throughout the child's life-time. We measured the economic consequences as costs per case, per death, and per disability-adjusted life year (DALY) averted. RESULTS: A routine JE immunization program was the most cost-effective strategy with a cost per DALYs averted of US$ 212.59 and US$ 94.09 from the government and societal perspectives respectively. In contrast, costs per DALYs averted through the JE vaccination campaign and introduction strategy was US$ 1,473.53 and US$ 1,224.20 from the government and societal perspectives respectively. CONCLUSIONS: Both JE vaccination strategies are cost-effective but they are not cost-saving when compared to no immunization program.

The spatial-temporal pattern of Japanese encephalitis and its influencing factors in Guangxi, China.

Japanese encephalitis (JE) is a major global public health threat. Using Japanese encephalitis incidence data from 2004 to 2010 in Guangxi Province, China, this study comprehensively explored the driving forces and the interactive effects between environmental and social factors of Japanese encephalitis using the Geo-detector method. The results indicated that the incidence of Japanese encephalitis showed a fluctuating downward trend from 2004 to 2010. The onset of JE was seasonal, mainly concentrated in June-July, and highly aggregated in northwestern Guangxi. Among the factors associated with Japanese encephalitis, days with temperatures >30 °C, accumulated temperatures >25 °C, slope, the normalized difference vegetation index, the gross domestic product of tertiary industries, the gross domestic product of primary industries and the number of pigs slaughtered showed higher contributions to Japanese encephalitis incidence. An enhanced interactive effect was found between environmental and social factors, and the interaction between days with humidity levels >80% and the gross domestic product of tertiary industries had the greatest combined effect on JE. These findings enhanced the understanding of the combined effect of social and environmental factors on the incidence of Japanese encephalitis and could help improve Japanese encephalitis transmission control and prevention strategies.

Effect of different vaccine strategies for the control of Japanese encephalitis in mainland China from 1961 to 2020: A quantitative analysis.

BACKGROUND: We aimed to quantify the impact of each vaccine strategy (including the P3-inactivated vaccine strategy [1968-1987], the SA 14-14-2 live-attenuated vaccine strategy [1988-2007], and the Expanded Program on Immunization [EPI, 2008-2020]) on the incidence of Japanese encephalitis (JE) in regions with different economic development levels. METHODS: The JE incidence in mainland China from 1961 to 2020 was summarized by year, then modeled and analyzed using an interrupted time series analysis. RESULTS: After the P3-inactivated vaccine was used, the JE incidence in Eastern China, Central China, Western China and Northeast China in 1968 decreased by 39.80 % (IRR = 0.602, P < 0.001), 7.80 % (IRR = 0.922, P < 0.001), 10.80 % (IRR = 0.892, P < 0.001) and 31.90 % (IRR = 0.681, P < 0.001); the slope/trend of the JE incidence from 1968 to 1987 decreased by 30.80 % (IRR = 0.692, P < 0.001), 29.30 % (IRR = 0.707, P < 0.001), 33.00 % (IRR = 0.670, P < 0.001) and 41.20 % (IRR = 0.588, P < 0.001). After the SA 14-14-2 live-attenuated vaccine was used, the JE incidence in Eastern China and Northeast China in 1988 decreased by 2.60 % (IRR = 0.974, P = 0.009) and 14.70 % (IRR = 0.853, P < 0.001); the slope/trend of the JE incidence in Eastern China and Central China from 1988 to 2007 decreased by 4.60 % (IRR = 0.954, P < 0.001) and 4.70 % (IRR = 0.953, P < 0.001). After the EPI was implemented, the JE incidence in Eastern China, Central China and Western China in 2008 decreased by 10.50 % (IRR = 0.895, P = 0.013), 18.00 % (IRR = 0.820, P < 0.001) and 24.20 % (IRR = 0.758, P < 0.001), the slope/trend of the JE incidence in Eastern China from 2008 to 2020 decreased by 17.80 % (IRR = 0.822, P < 0.001). CONCLUSIONS: Each vaccine strategy has different effects on the JE incidence in regions with different economic development. Additionally, some economically underdeveloped regions have gradually become the main areas of the JE outbreak. Therefore, mainland China should provide economic assistance to areas with low economic development and improve JE vaccination plans in the future to control the epidemic of JE.

The epidemiology and disease burden of children hospitalized for viral infections within the family Flaviviridae in China: A national cross-sectional study.

BACKGROUND: Viruses of the family Flaviviridae, including Japanese encephalitis virus (JEV), dengue virus (DENV), yellow fever virus (YFV) and hepatitis C virus (HCV), are widely distributed worldwide. JEV, DENV and YFV belong to the genus Flavivirus, whereas HCV belongs to the genus Hepacivirus. Children's symptoms are usually severe. As a result, rates of hospitalization due to infection with these viruses are high. The epidemiology and disease burden of hospitalized children have rarely been described in detail to date. The objective of this study was to report the general epidemiological characteristics, clinical phenotype, length of stay (LOS), burden of disease, and potential risk factors for hospitalized children infected with JEV, DENV, YFV, or HCV in Chinese pediatric hospitals. METHODOLOGY: A cross-sectional study of epidemiology and disease burden of children hospitalized for Flaviviridae virus infections between December 2015 and December 2020 in China was performed. Face sheets of discharge medical records (FSMRs) were collected from 27 tertiary children's hospitals in the Futang Research Center of Pediatric Development and aggregated into FUTang Update medical REcords (FUTURE). Information on sociodemographic variables, clinical phenotype, and LOS as well as economic burden was included in FSMRs and compared using appropriate statistical tests. FINDINGS: The study described 490 children aged 0-15 years hospitalized for infections with Flaviviridae viruses. Japanese encephalitis (JE) cases are the highest, accounting for 92.65% of the total hospitalization cases caused by Flaviviridae virus infection. The incidence of JE peaked from July to October with a profile of a high proportion of severe cases (68.06%) and low mortality (0.44%). Rural children had a significantly higher incidence than urban children (91.63%). Most hospitalized dengue cases were reported in 2019 when dengue outbreaks occurred in many provinces of China, although only 14 dengue cases were collected during the study period. Yellow fever (YF) is still an imported disease in China. The hospitalizations for children with hepatitis C (HC) were not high, and mild chronic HC was the main clinical phenotype of patients. Among the four viral infections, JE had the highest disease burden (LOS and expenditure) for hospitalized children. CONCLUSION: First, the present study reveals that JE remains the most serious disease due to Flaviviridae virus infection and threatens children's health in China. Many pediatric patients have severe illnesses, but their mortality rate is lower, suggesting that existing treatment is effective. Both JEV vaccination and infection control of rural children should represent a focus of study. Second, although the dual risks of indigenous epidemics and imports of DENV still exist, the prevalence of DENV in children is generally manageable. Third, YFV currently shows no evidence of an epidemic in China. Finally, the proportion of children with chronic hepatitis C (CHC) is relatively large among hospitalized children diagnosed with HCV. Thus, early and effective intervention should be offered to children infected with HCV to ease the burden of CHC on public health.

Impact of the expanded program on immunization on the incidence of Japanese encephalitis in different regions of Mainland China: An interrupt time series analysis.

In 2008, Mainland China included the Japanese encephalitis (JE) vaccine in the Expanded Program on Immunization (EPI) to control the JE epidemic. However, Northwest China experienced the largest JE outbreak since 1994 in 2018, and the effects of the EPI in different regions are unclear. Therefore, we used an interrupted time series design to evaluate the effects of the EPI in different regions. In this study, ß1 and ß1+ß3 represented the slope or trend of the JE incidence before and after the EPI, respectively; ß2 was the level change of the JE incidence immediately after the EPI; ß3 represented the slope change of the JE incidence before and after the EPI. We found that the JE incidence in all regions showed a decreasing trend before the EPI (ß1<0.000, P<0.05). The JE incidence in Mainland China (ß2=-7.669, P<0.05), East China (ß2=-9.791, P<0.05), Central China (ß2=-10.695, P<0.05), South China (ß2=-6.551, P<0.05) and Southwest China (ß2=-2.216, P<0.05) decreased by 7.669/100,000, 9.791/100,000, 10.695/100,000, 6.551/100,000 and 2.216/100,000 immediately after the EPI, and the EPI had short-term effects on the JE incidence in these regions. The slope of the JE incidence in Mainland China (ß3=0.272, P<0.05), East China (ß3=0.337, P<0.05), Central China (ß3=0.381, P<0.05), South China (ß3=0.254, P<0.05) and Southwest China (ß3=0.081, P<0.05) increased by 0.272, 0.337, 0.381, 0.254 and 0.081 after the EPI, and the EPI had long-term effects on the JE incidence in these regions. The JE incidence in many regions (excluding North China) showed a decreasing trend after the EPI (ß1+ß3 <0.000). Northwest China (GDP from 2008 to 2020 ranked last in Mainland China) and Southwest China (GDP from 2008 to 2020 ranked fifth in Mainland China), with underdeveloped economy, used to be low-epidemic regions of JE, but they have become high-epidemic regions in recent years. Economic development may contribute to the geographic variations in the effects of the EPI. Therefore, it is significant for JE control in Mainland China to increase support for underdeveloped regions and adjust the vaccine strategy according to the new epidemic situation of JE.

Long-Term Neurological Sequelae and Disease Burden of Japanese Encephalitis in Gansu Province, China.

Background and objects: The study aimed to evaluate the long-term neurological sequelae and the disease burden of JE in Gansu, China. Methods: JE patients were included as study population from 2005-2011 in Gansu, and a follow-up survey was conducted in 2007-2014. Pair-matched healthy individuals were selected as controls. All subjects underwent a neurological examination and intelligence quotient (IQ) and memory quotient (MQ) assessments. Then, the disability-adjusted life years (DALYs), and direct and indirect medical expenses were systematic assessed. Results: Forty-four point seven percent of the JE patients had objective neurological deficits, compared with 2.4% of controls. Subnormal intelligence was found in 21.2% of JE subjects, compared with 1.2% control who exhibited a mildly reduced IQ. Abnormal MQ scores were noted in 56.3% JE subjects, compared with only 12.7% controls. Prevalence of each sequelae caused by JE were significantly higher in adults than in younger subjects. Furthermore, median DALY lost due to JE was 9.2 per subject. Median economic cost of JE was approximately $2776.6 per subject and significantly higher in adults than in younger subjects. Findings and Conclusions: JE patients suffered from severe neurological sequelae and high disease burden, resulting in a significant downstream burden for both the patients (especially adults) and the healthcare system.

Impact of cattle on joint dynamics and disease burden of Japanese encephalitis and leptospirosis.

Japanese encephalitis (JE) is a mosquito-borne neglected tropical disease. JE is mostly found in rural areas where people usually keep cattle at home for their needs. Cattle in households reduce JE virus infections since they distract vectors and act as a dead-end host for the virus. However, the presence of cattle introduces risk of leptospirosis infections in humans. Leptospirosis is a bacterial disease that spreads through direct or indirect contact of urine of the infected cattle. Thus, cattle have both positive and negative impacts on human disease burden. This study uses a mathematical model to study the joint dynamics of these two diseases in the presence of cattle and to identify the net impact of cattle on the annual disease burden in JE-prevalent areas. Analysis indicates that the presence of cattle helps to reduce the overall disease burden in JE-prevalent areas. However, this reduction is dominated by the vector's feeding pattern. To the best of our knowledge, this is the first study to examine the joint dynamics of JE and leptospirosis.

Economic and disease burden of Japanese encephalitis in Zhejiang Province, 2013-2018.

BACKGROUND: Japanese encephalitis (JE) is a mosquito-borne disease and associated with high mortality and disability rate among symptomatic cases. In the absence of local data, this study estimated the economic burden and the disability-adjusted life years (DALYs) due to JE in Zhejiang Province, China during 2013-2018, to increase disease awareness and provide evidence for effective health policy. METHODOLOGY/PRINCIPLE FINDINGS: We merged multiple data sources, including National Notifiable Disease Registry System (NNDRS), patient interviews and medical records from corresponding hospitals for JE cases which occurred during 2013-2018 in Zhejiang Province. Direct costs were extracted from hospitals' billing systems and patient interviews. Indirect costs and disease burden were calculated based on questionnaire survey from patient interviews and follow-up assessment by general practitioners. Given under-reporting, an expansion factor (EF) was applied to extrapolate the JE burden to the provincial level. The total economic burden of JE during 2013-2018 was estimated at US $12.01 million with an EF = 3. Of this, $8.32 million was due to direct economic cost and $3.69 million to indirect cost. The disease burden of JE was 42.75 DALYs per million population (28.44 YLD, 14.28 YLL) according to the 1990 Global Burden of Disease (GBD 1990) methodology and 80.01 DALYs (53.67YLD, 26.34YLL) according to the GBD 2010 methodology. Sensitivity analysis demonstrated that the overall economic burden varied from US$ 1.73-36.42 million. The greatest variation was due to the prognosis of illness (-85.57%-203.17%), followed by occupation (-34.07%-134.12%) and age (-72.97%-47.69%). CONCLUSIONS/SIGNIFICANCE: JE imposes a heavy burden for families and society in Zhejiang Province. This study provides comprehensive empirical estimates of JE burden to increase awareness and strengthen knowledge of the public. These data may support provincial level public health decision making for prevention and control of JE. Ongoing surveillance for acute meningitis and encephalitis syndrome (AEMS) in sentinel hospitals, is needed to further refine estimates of JE burden.

Assessment of effectiveness of Japanese encephalitis vaccination in West Bengal, India using sample positivity rate as an alternate measure.

BACKGROUND & OBJECTIVES: Japanese encephalitis (JE), is a vaccine preventable mosquito borne arboviral disease. The State Health Department of West Bengal, India started a vaccination programme using live attenuated, single dose JE vaccine (SA-14-14-2) in children aged 1-below15 years since 2006 in five districts. The objectives were to compare Sample Positivity Rates (SPR) of Acute Encephalitis Syndrome (AES) cases for JE between vaccinated & unvaccinated districts and observe trend of SPR & Cumulative Incidence in vaccinated districts for three years. METHODS: The study was based on the analysis of surveillance data from all tested AES cases including confirmed JE (IgM ELISA) from all JE testing facilities existent in the state during the study period (2011-13). Calculation of Cumulative Incidence, Odds Ratio (OR) with 95% CI, Preventive Fraction and Chi Square for trend (for SPR) was done. Trend of incidence was assessed by linear regression. RESULTS: In three years, 5 vaccinated districts contributed 945 AES and 88 JE cases (SPR - 9.3%) compared to 1807 and 254 (SPR - 14.1%) JE cases in 14 unvaccinated districts. Effectiveness of vaccination was evident by gradual decline of Odds Ratio in favour of vaccinated districts. Vaccination effectiveness of 68% overall and 80% [OR = 0.20 (0.10 - 0.41)] in below 15 years were observed. Trend of SPR was found significantly declining in most of the vaccinated districts. INTERPRETATION & CONCLUSION: Significant reduction in sample positivity rate over three years in most of the vaccinated districts indicated that the vaccination programme had been gradually effective.

Hospital-based surveillance for Japanese encephalitis in Bangladesh, 2007-2016: Implications for introduction of immunization.

BACKGROUND: Japanese encephalitis (JE) virus is recognized as a major cause of encephalitis in Bangladesh. The World Health Organization (WHO) recommends human immunization as the most effective means to control JE. Several WHO-prequalified vaccines are available to prevent JE but no vaccination program has been implemented in Bangladesh. METHODS: We conducted hospital-based surveillance for acute meningitis-encephalitis syndrome (AMES) to describe JE epidemiology and help inform policy decisions about possible immunization strategies for Bangladesh. RESULTS: During 2007-2016, a total of 6543 AMES patients were identified at four tertiary hospitals. Of the 6525 patients tested, 548 (8%) were classified as JE cases. These 548 patients resided in 36 (56%) out of 64 districts of Bangladesh, with the highest proportion of JE cases among AMES patients (12% and 7%) presenting at two hospitals in the northwestern part of the country. The median age of JE cases was 30 years, and 193 (35%) were aged ≤15 years. The majority of JE cases (80%) were identified from July through November. CONCLUSIONS: Surveillance results suggest that JE continues to be an important cause of meningo-encephalitis in Bangladesh. Immunization strategies including JE vaccine introduction into the routine childhood immunization program or mass vaccination in certain age groups or geographic areas need to be examined, taking into consideration the cost-effectiveness ratio of the approach and potential for decreasing disease burden.

Estimates of the global burden of Japanese encephalitis and the impact of vaccination from 2000-2015.

Japanese encephalitis (JE) is a mosquito-borne disease, known for its high mortality and disability rate among symptomatic cases. Many effective vaccines are available for JE, and the use of a recently developed and inexpensive vaccine, SA 14-14-2, has been increasing over the recent years particularly with Gavi support. Estimates of the local burden and the past impact of vaccination are therefore increasingly needed, but difficult due to the limitations of JE surveillance. In this study, we implemented a mathematical modelling method (catalytic model) combined with age-stratifed case data from our systematic review which can overcome some of these limitations. We estimate in 2015 JEV infections caused 100,308 JE cases (95% CI: 61,720-157,522) and 25,125 deaths (95% CI: 14,550-46,031) globally, and that between 2000 and 2015 307,774 JE cases (95% CI: 167,442-509,583) were averted due to vaccination globally. Our results highlight areas that could have the greatest benefit from starting vaccination or from scaling up existing programs and will be of use to support local and international policymakers in making vaccine allocation decisions.

Comparative economic analysis of strategies for Japanese encephalitis vaccination of U.S. travelers.

BACKGROUND: Japanese encephalitis (JE) virus is the leading vaccine-preventable cause of encephalitis in Asia. For most travelers, JE risk is very low but varies based on several factors, including travel duration, location, and activities. To aid public health officials, health care providers, and travelers evaluate the worth of administering/ receiving pre-travel JE vaccinations, we estimated the numbers-needed-to-treat to prevent a case and the cost-effectiveness ratios of JE vaccination for U.S. travelers in different risk categories. METHODS: We used a decision tree model to estimate cost per case averted from a societal and traveler perspective for hypothetical cohorts of vaccinated and unvaccinated travelers. Risk Category I included travelers planning to spend ≥1 month in JE-endemic areas, Risk Category II were shorter-term (<1 month) travelers spending ≥20% of their time doing outdoor activities in rural areas, and Risk Category III were all remaining travelers. We performed sensitivity analyses including examining changes in cost-effectiveness with 10- and 100-fold increases in incidence and medical treatment costs. RESULTS: The numbers-needed-to-treat to prevent a case and cost per case averted were approximately 0.7 million and $0.6 billion for Risk Category I, 1.6 million and $1.2 billion for Risk Category II, and 9.8 million and $7.6 billion for Risk Category III. Increases of 10-fold and 100-fold in disease incidence proportionately decreased cost-effectiveness ratios. Similar levels of increases in medical treatment costs resulted in negligible changes in cost-effectiveness ratios. CONCLUSION: Numbers-needed-to-treat and cost-effectiveness ratios associated with preventing JE cases in U.S. travelers by vaccination varied greatly by risk category and disease incidence. While cost effectiveness ratios are not the sole rationale for decision-making regarding JE vaccination, the results presented here can aid in making such decisions under very different risk and cost scenarios.

Japanese encephalitis vaccination in the Philippines: A cost-effectiveness analysis comparing alternative delivery strategies.

INTRODUCTION: Japanese encephalitis (JE) is a mosquito-borne viral infection of the brain that can cause permanent brain damage and death. In the Philippines, efforts are underway to deliver a live attenuated JE vaccine (CD-JEV) to children under five years of age (YOA), who are disproportionately infected. Multiple vaccination strategies are being considered. METHODS: We conducted a cost-effectiveness analysis comparing three vaccination strategies to the current state of no vaccination from the societal and government perspectives: (1) national routine vaccination only, (2) sub-national campaign followed by national routine, and (3) national campaign followed by national routine. We developed a Markov model to estimate impact of vaccination or no vaccination over the child's lifetime horizon, assuming an annual incidence of 10.6 cases per 100,000. Costs of illness ($859/case), vaccine ($0.50/dose), routine vaccination ($0.95/dose), and campaign vaccination ($0.98/dose) were based on hospital financial records, expert opinion and literature. The societal perspective included transportation and opportunity costs of caregiver time, in addition to costs incurred by the health system. RESULTS: JE vaccination via national campaign followed by national routine delivery was the most cost-effective strategy modeled with a cost per disability adjusted life year (DALY) averted of $233 and $29 from the government and societal perspectives, respectively. Results were similar for other delivery strategies with cost/DALY ranging from $233 to $265 from the government perspective and $29-$57 from the societal perspective. JE vaccination was projected to prevent 27,856-37,277 cases, 5571-7455 deaths, and 173,233-230,704 DALYs among children under five over 20 consecutive birth cohorts. Total incremental costs of vaccination versus no vaccination over 20 birth cohorts were $6.6-$9.8 million from the societal perspective ($230 K-$440 K annually) and $45.9-$53.9 million ($2.2 M-$2.7 M annually) from the governmental perspective. CONCLUSION: Vaccination with CD-JEV in the Philippines is projected to be cost-effective, reducing long-term costs associated with JE illness and improving health outcomes compared to no vaccination.

Introduction of the Japanese encephalitis virus (JEV) in the United States - A qualitative risk assessment.

The purpose of this risk assessment (RA) was to qualitatively estimate the risk of emergence of the Japanese encephalitis virus (JEV) in the United States (US). We followed the framework for RA of emerging vector-borne livestock diseases (de Vos et al. 2011), which consists of a structured questionnaire, whose answers to questions can be delivered in risk categories, descriptive statements, or yes or no type of answers, being supported by the literature. The most likely pathways of introduction of JEV identified were: (a) entry through infected vectors (by aircraft, cargo ships, tires, or wind); (b) import of infected viremic animals; (c) entry of viremic migratory birds; (d) import of infected biological materials; (e) import of infected animal products; (f) entry of infected humans; and (g) import/production of contaminated biological material (e.g., vaccines). From these pathways, the probability of introduction of JEV through infected adult mosquitoes via aircraft was considered very high and via ships/containers was deemed low to moderate. The probability of introduction via other pathways or modes of entry (vector eggs or larvae, hosts, and vaccines) was considered negligible. The probability of transmission of JEV was variable, ranging from low to high (in the presence of both competent vectors and hosts), depending on the area of introduction within the US. Lastly, the probability of establishment of JEV in the continental US was considered negligible. For that reason, we stopped the risk assessment at this point of the framework. This RA provides important information regarding the elements that contribute to the risk associated with the introduction of JEV in the US. This RA also indicates that infected mosquitoes transported in aircraft (and cargo ships) are the most likely pathway of JEV entry and therefore, mitigation strategies should be directed towards this pathway.

Analysis of the Full Economic Cost for Japanese Encephalitis Under Different Risk Scenarios for Business Travelers to Asia.

OBJECTIVE: Methods for assessing the costs and benefits of administering vaccines to international business/occupational travelers, assignees, and expatriates have neglected the impact of health and treatment on work productivity. The research objective is to evaluate the benefit to cost ratio of the Japanese encephalitis (JE) vaccine for international business/occupational travelers to Asia and other endemic areas incorporating a health and productivity approach. METHODS: Costs and benefits were estimated using actuarial methods with data obtained from secondary sources describing prevalence of infection risk and health outcomes, and business traveler demographic and travel characteristics. Results assumed 2018 salaries and prices, with employee time valued according to total compensation. RESULTS: Risks contracting JE vary widely on the basis of length of trip, season, and destination. The productivity benefits of vaccinating a traveler outweigh the vaccination costs for those staying 30 days or longer in endemic areas during one or more transmission seasons ($2009 vs $750 per traveler), and for business travelers to endemic areas during the transmission season with outdoor activities for the average 2-week/15.4-day international business trip ($502 to $815 vs $500). Vaccination costs outweigh the productivity benefits for short-term travelers who remain in urban areas or travel outside of the transmission season ($10 vs $500). CONCLUSION: JE Vaccination for business travelers in the active transmission season has a net benefit under certain conditions that are not commonly considered risky, such as average-length trips to peri-urban areas, in situations where contracting disease would result in significant business disruption, or when multiple trips are anticipated over several years.

A quantitative risk assessment (QRA) of the risk of introduction of the Japanese encephalitis virus (JEV) in the United States via infected mosquitoes transported in aircraft and cargo ships.

Following a qualitative risk assessment, in which we identified and assessed all viable pathways for the introduction of the Japanese encephalitis virus (JEV) into the United States (US), we identified entry through infected vectors via aircraft and cargo ships as the most likely pathway, and thus considered it further in a quantitative risk assessment (QRA) model. The objective of this study was to evaluate the risk of introduction of JEV in the US via infected mosquitoes transported in aircraft and cargo ships arriving from Asia, using a QRA model. We created a stochastic model to quantify the probability of introduction of at least one infected mosquito in the continental US via aircraft and cargo ships, per at-risk period (March to October) or year, respectively. We modeled the following parameters: number of flights (per at-risk period, i.e., March to October) and cargo ships (per year) and per region, number of mosquitoes per flight and ship, number of mosquitoes that were not found and sensitivity of the mosquito collection method in aircraft, mosquito infection rates, and number of mosquitoes coming in aircraft per at-risk period (March to October) and cargo ships per year. Flight and cargo ship data pertained to years 2010-2016. For model building purposes, we only considered port-to-port vessels arriving from Asia to the US, we assumed that mosquitoes survive the trans-Pacific Ocean ship crossing and that the number of mosquitoes in cargo and passenger flights is similar. Our model predicted a very high risk (0.95 median probability; 95% CI = 0.80-0.99) of at least one infected mosquito being introduced in the US during the at-risk period, i.e., March to October, via aircraft transportation from JEV-affected countries in Asia. We also estimated that a median of three infected mosquitoes can enter the US during the at-risk period, i.e., March to October (95% CI = 1-7). The highest probability of introduction via aircraft was attributed to the Mediterranean California ecoregion (0.74; 95% CI = 0.50-0.90). We predicted, however, a negligible risk (0; 95% CI = 0.00-0.01) of at least one infected mosquito being introduced via cargo ships. Although the risk of introduction of JEV-infected mosquitoes by cargo ships was negligible, the risk via aircraft was estimated to be high. Our findings indicate the need to prioritize JEV prevention and control methods for aircraft-based pathways, such as aircraft disinfection. The quantitative estimates provided in this study are of interest to public health entities and other stakeholders, as they may support future interventions for preventing JEV introduction, as well as other vector-borne diseases, in the US and other countries.

How much does direct transmission between pigs contribute to Japanese Encephalitis virus circulation? A modelling approach in Cambodia.

Japanese Encephalitis (JE) is the most important cause of human encephalitis throughout Asia and the Pacific. Although JE is a vector-borne disease, it has been demonstrated experimentally that transmission between pigs can occur through direct contact. Whether pig-to-pig transmission plays a role in the natural epidemiological cycle of JE remains unknown. To assess whether direct transmission between pigs may occur under field conditions, we built two mathematical models of JE transmission incorporating vector-borne transmission alone or a combination of vector-borne and direct transmission. We used Markov Chain Monte Carlo (MCMC) techniques to estimate the parameters of the models. We fitted the models to (i) two serological datasets collected longitudinally from two pig cohorts (C1 and C2) during two periods of four months on a farm on the outskirts of Phnom-Penh, Cambodia and to (ii) a cross-sectional (CS) serological survey dataset collected from 505 swine coming from eight different provinces of Cambodia. In both cases, the model incorporating both vector-borne and direct transmission better explained the data. We computed the value of the basic reproduction number R0 (2.93 for C1, 2.66 for C2 and 2.27 for CS), as well as the vector-borne reproduction number Rpv and the direct transmission reproduction number Rpp. We then determined the contribution of direct transmission on R0 (11.90% for C1, 11.62% for C2 and 7.51% for CS). According to our results, the existence of pig-to-pig transmission is consistent with our swine serological data. Thus, direct transmission may contribute to the epidemiological cycle of JE in Cambodia. These results need to be confirmed in other eco-climatic settings, in particular in temperate areas where pig-to-pig transmission may facilitate the persistence of JE virus (JEV) during cold seasons when there are no or few mosquitoes.