Modelling Japanese encephalitis virus transmission dynamics and human exposure in a Cambodian rural multi-host system.

Japanese encephalitis (JE) is a vector-borne zoonosis and the leading cause of human viral encephalitis in Asia. Its transmission cycle is usually described as involving wild birds as reservoirs and pigs as amplifying hosts. JE is endemic in Cambodia, where it circulates in areas with low pig densities (<70 pigs per km2), and could be maintained in a multi-host system composed of pigs, but also poultry as competent hosts, and dogs, cattle and humans as non-competent hosts. We used a mathematical model representing Japanese encephalitis virus (JEV) transmission in a traditional Cambodian village that we calibrated with field data collected in 3 districts of Kandal province, Cambodia. First, R0 calculations allowed us to assess the capacity of the epidemiological system to be invaded by JEV and sustain virus transmission in villages in the 3 districts, and we predicted human exposure at the epidemiological equilibrium, based on simulations. Changes in spatial density of livestock, in agricultural practices, and epizootics (e.g., African swine fever), can profoundly alter the composition of host communities, which could affect JEV transmission and its impact on human health. In a second step, we then used the model to analyse how host community composition affected R0 and the predicted human exposure. Lastly, we evaluated the potential use of dog JE seroprevalence as an indicator of human exposure to JEV. In the modeled villages, the calculated R0 ranged from 1.07 to 1.38. Once the equilibrium reached, predicted annual probability of human exposure ranged from 9% to 47%, and predicted average age at infection was low, between 2 and 11 years old, highlighting the risk of severe forms of JEV infection and the need to intensify child immunization. According to the model, increasing the proportion of competent hosts induced a decrease in age at infection. The simulations also showed that JEV could invade a multi-host system with no pigs, reinforcing the assumption of poultry acting as reservoirs. Finally, the annual human exposure probability appeared linearly correlated with dog seroprevalence, suggesting that in our specific study area, dog seroprevalence would be a good proxy for human exposure.

Comparison of Japanese Encephalitis Force of Infection in Pigs, Poultry and Dogs in Cambodian Villages.

Japanese encephalitis virus (JEV) is the main cause of human viral encephalitis in Asia, with a mortality rate reaching 30%, mostly affecting children. The traditionally described cycle involving wild birds as reservoirs, pigs as amplifying hosts and Culex mosquitoes as vectors is questioned, with increasing evidence of a more complex multi-host system involved in areas where densities of pigs are low, such as in Cambodia. In 2018, we examined pigs, chickens, ducks and dogs from Kandal province, Cambodia, for antibody response against JEV by hemagglutination inhibition and virus neutralization assays. Forces of infection (FOI) for flaviviruses and JEV were estimated per species and per unit of body surface area (BSA). JEV seroprevalence reached 31% (95% CI: 23-41%) in pigs, 1% (95% CI: 0.1-3%) in chickens, 12% (95% CI: 7-19%) in ducks and 35% (95% CI: 28-42%) in dogs. Pigs were most likely to be infected (FOI: 0.09 per month), but the FOI was higher in ducks than in pigs for a given BSA (ratio of 0.13). Dogs had a lower FOI than ducks but a higher FOI than chickens (0.01 per month). For a given BSA, dogs were less likely to be infected than pigs (ratio of 1.9). In Cambodia, the virus may be circulating between multiple hosts. Dogs live in close contact with humans, and estimating their exposure to JEV infection could be a relevant indicator of the risk for humans to get infected, which is poorly known due to underdiagnosis. Understanding the JEV cycle and developing tools to quantify the exposure of humans is essential to adapt and support control measures for this vaccine-preventable disease.

Serological Evidence for Japanese Encephalitis and West Nile Virus Infections in Domestic Birds in Cambodia.

Mosquito-borne flaviviruses with an enzootic transmission cycle like Japanese encephalitis virus (JEV) and West Nile virus (WNV) are a major public health concern. The circulation of JEV in Southeast Asia is well-documented, and the important role of pigs as amplification hosts for the virus is long known. The influence of other domestic animals especially poultry that lives in high abundance and close proximity to humans is not intensively analyzed. Another understudied field in Asia is the presence of the closely related WNV. Such analyses are difficult to perform due to the intense antigenic cross-reactivity between these viruses and the lack of suitable standardized serological assays. The main objective of this study was to assess the prevalence of JEV and WNV flaviviruses in domestic birds, detailed in chickens and ducks, in three different Cambodian provinces. We determined the flavivirus seroprevalence using an hemagglutination inhibition assay (HIA). Additionally, we investigated in positive samples the presence of JEV and WNV neutralizing antibodies (nAb) using foci reduction neutralization test (FRNT). We found 29% (180/620) of the investigated birds positive for flavivirus antibodies with an age-depended increase of the seroprevalence (OR = 1.04) and a higher prevalence in ducks compared to chicken (OR = 3.01). Within the flavivirus-positive birds, we found 43% (28/65) with nAb against JEV. We also observed the expected cross-reactivity between JEV and WNV, by identifying 18.5% double-positive birds that had higher titers of nAb than single-positive birds. Additionally, seven domestic birds (10.7%) showed only nAb against WNV and no nAb against JEV. Our study provides evidence for an intense JEV circulation in domestic birds in Cambodia, and the first serological evidence for WNV presence in Southeast Asia since decades. These findings mark the need for a re-definition of areas at risk for JEV and WNV transmission, and the need for further and intensified surveillance of mosquito-transmitted diseases in domestic animals.

How Central Is the Domestic Pig in the Epidemiological Cycle of Japanese Encephalitis Virus? A Review of Scientific Evidence and Implications for Disease Control.

Despite the existence of human vaccines, Japanese encephalitis (JE) remains the leading cause of human encephalitis in Asia. Pigs are described as the main amplifying host, but their role in JE epidemiology needs to be reassessed in order to identify and implement efficient control strategies, for both human and animal health. We aimed to provide a systematic review of publications linked to JE in swine, in terms of both individual and population characteristics of JE virus (JEV) infection and circulation, as well as observed epidemiological patterns. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to select and analyze relevant articles from the Scopus database, 127 of which were included in the review. Pigs are central, but the implication of secondary hosts cannot be ruled out and should be further investigated. Although human vaccination cannot eradicate the virus, it is clearly the most important means of preventing human disease. However, a better understanding of the actual involvement of domestic pigs as well as other potential JEV hosts in different JEV epidemiological cycles and patterns could help to identify additional/complementary control measures, either by targeting pigs or not, and in some specific epidemiological contexts, contribute to reduce virus circulation and protect humans from JEV infection.

In silico Comparison of Test-and-Cull Protocols for Bovine Tuberculosis Control in France.

Whole depopulation of cattle herds (WHD) confirmed infected by bovine tuberculosis (bTB) has led since the 1950s to a drop of herd incidence in France below 0.1% in 2000, justifying the current officially bTB free (OTF) status of the country. However, this protocol is expensive, ethically questionable, and difficult for breeders to accept because the number of confirmed animals in an infected herd is often very low. A test-and-cull protocol combining at least three screening sessions of the entire herd followed by the slaughter of all the non-negative animals has been used for some years. The aim of this work was to evaluate in silico the epidemiological effectiveness, the public costs and the acceptability to farmers of this test-and-cull protocol as well as of several ones. A stochastic compartmental model of within-herd bTB spread was used. Six test-and-cull protocols were compared: two versions of the official protocol and four alternatives with varying delays between screenings, and varying tests used. Protocols were simulated for an average French beef herd, and compared to WHD. Three key indicators were computed: the failure probability of the protocol (a failure being defined as an herd recovering its OTF status recovery while still infected, indicator of epidemiological effectiveness), its overall public cost and the percentage of farmers who would have dropped it to switch to WHD (indicator of acceptability to farmers). Failure probability ranged from 1.4 to 12.4% and was null (by definition) for WHD. The median cost varied between 2.7 and 78 K€ for the test-and-cull protocols, vs. 120 K€ for WHD. The percentage of dropout ranged from 7.8 to 22%. The optimal tradeoff between epidemiological effectiveness, public costs, and acceptability to farmers was obtained for protocols with an increased delay (6 months instead of 2 in the currently used protocol) between the last two screening sessions, with either 3 or 2 screening sessions. This study may help improving the official test-and-cull protocol applied in France under European Union regulation, by suggesting alternative protocols, very effective, cheaper, and more acceptable than WHD.