SHIC-Funded Systematic Literature Review Reveals JEV Knowledge Gaps

Due to the ongoing risk of Japanese encephalitis virus emergence in the US, the Swine Health Information Center funded a systematic literature review intended to increase understanding of the virus’s biology, components and dynamics of transmission, and environmental factors necessary for incursion and establishment. The recently completed systematic review is in addition to a separate JEV Risk Assessment funded by SHIC that is still in progress. As the US is considered a susceptible region with potential for the introduction of JEV, SHIC has focused on these projects designed to further strengthen US swine industry preparedness and inform response efforts, should they be needed.

Led by Dr. Natalia Cernicchiaro, Kansas State University, and in collaboration with researchers from the United States Department of Agriculture National Bio and Agro-Defense facility and the National Feral Swine Damage Management Program, the study synthesized existing information on the role of domestic and feral swine in the transmission of JEV through a systematic review of 228 articles deemed relevant in a process designed to identify knowledge gaps.

In results delivered to SHIC in June 2023, Dr. Cernicchiaro and colleagues provided information on US susceptibility to JEV related to the availability of competent mosquito vector species, susceptible maintenance avian hosts, as well as intensive travel and trade activities to and from Japanese encephalitis-affected countries. Additional information relevant to US risk is described, such as the similar climatic and environmental conditions to epidemic countries, lack of JEV surveillance, and the large populations of susceptible swine which can serve as amplification hosts. The considerable geographical expansion of JEV in recent decades, including the recent emergence of a new genotype in the eastern and southeastern Australian states, adds to US pork industry concern.

Relevant findings are included in the study summary and include the following.

JEV in swine is generally mild with a neurologic or reproductive presentation depending on the age and sex of the pigs. Although maternal antibodies can confer protection for longer than four months under field conditions, naïve piglets can manifest neurologic signs including ataxia and tremors which can progress to wasting disease or mortality. Reproductive disorders including stillbirths, abortions, mummified fetuses, and delayed farrowing can occur when sows are infected before 60 to 70 days of gestation. Orchitis, reduced sperm motility and temporary infertility have been reported in boars.

Typically, JEV infection is initiated following the bite of an infected mosquito. In the blood, the virus can be detected as early as one day post-infection and can persist for four to five days, regardless of the portal of entry. Once pigs are exposed to the virus, on average it takes three to six days, and up to 21 days, to observe clinical signs. Amplification and persistence mechanisms, as well as the effect of genotype in infectivity, transmission and pathogenesis in swine need to be better explained.

Recent evidence suggests that direct contact between pigs may also play a role in transmission, yet additional research is needed to ensure replication of those findings and further evaluate its implications for pathogenesis and spread. 

Serological testing followed by virus isolation for confirmation is recommended for diagnosis. During outbreak investigations, serial collection of serum samples in pigs is used to detect an increasing titer against JEV. Different tissues are amenable for virus isolation including spleen, liver, brain, sera, cerebrospinal fluid, tonsils, and oronasal fluids. In fetuses, stillbirths or neonates, virus may be isolated from brain, tonsil, spleen, placenta, thoracic or abdominal stillborn fluids. Serologic tests that demonstrate antibodies in fetuses also are useful in diagnosis.

Given no specific therapy is available for treating JEV infection in pigs, control either via mitigation of reproductive losses by vaccination or application of biosecurity practices is critical. Articles describing biosecurity practices for control and risk management at the farm level were very limited. Practices include the application and effectiveness of mosquito control and other pest management practices.

Vaccination against JEV is the most effective measure for controlling JEV in humans and pigs. Although there are no licensed JEV vaccines for pigs in the US, live attenuated vaccines have shown higher efficacy than inactivated vaccines in natural infection and challenge studies. Vaccinating the breeding stock can control viral amplification and reproductive disease in swine. Before the mosquito season starts, young gilts and boars can be vaccinated twice with a 14 to 21 day interval. In endemic areas, growing pigs are also often vaccinated.

Evidence on risk factors for JEV morbidity pertaining to pigs and their production environment, genetic, sex, and breed differences, as well as management practices at the farm, barn or animal levels, among others, were infrequent to nonexistent. Although some studies reported the use of pigs as sentinels of infection, the design, implementation, and effectiveness of surveillance programs in pigs was rarely described. Even though no peer-reviewed articles were retrieved on preparedness and response efforts related to pigs, national response plans for the animal and human health sectors from governments or other official entities are available from some countries where JEV is present.

Of note are all the resources and educational materials produced in response to the most recent JEV outbreaks by the Australian Government, Department of Health and Aged Care, including the Joint National JEV Outbreak response plan published in June 2023 (JEV outbreak plan). Economic assessments associated with swine, either domestic or feral, and JEV transmission, at the regional, country, state or farm levels were not identified with the search. Similarly, articles discussing impacts or implications of JE in pigs or swine operations were not available.

Pigs have a unique role in the JEV transmission cycle as they can exhibit clinical signs of reproductive and neurological disease, as well as produce sufficient viremia to infect biting mosquito vectors.  Provided in this review, knowledge of the dynamics of the disease process, modes of viral transmission, risks associated with infection, control and treatment options, as well as potential impacts of the disease in swine production, may inform researchers, stakeholders, and policy makers on effort prioritization and development of preparedness and response measures.  

The full report will be available following publication in a scientific journal.

The Swine Health Information Center, launched in 2015 with Pork Checkoff funding, protects and enhances the health of the US swine herd by minimizing the impact of disease threats through preparedness, coordinated communications, global disease monitoring, analysis of swine health data, and targeted research investments. As a conduit of information and research, SHIC encourages sharing of its publications and research. Forward, reprint, and quote SHIC material freely. For more information, visit http://www.swinehealth.org or contact Dr. Paul Sundberg at [email protected] or Dr. Megan Niederwerder at [email protected].