The skip-and-resurgence of Japanese encephalitis: new virus strain invasion in Southeast Asia

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What is Japanese encephalitis virus?
Japanese encephalitis virus (JEV) is a zoonotic mosquito-borne virus, persisting mainly in pigs, Ardeid birds and Culex mosquitoes. JEV is mainly transmitted via mosquitos, almost all human infections are due to mosquito bites by insects that have bitten JEV-infected reservoirs (e.g., pigs and birds) recently.

Most infections occur asymptomatically or with mild symptoms such as fever and headache. More severe infection is characterized by rapid onset of headache, high fever, neck stiffness, impaired mental state, coma, tremors, convulsions (especially in children) and paralysis [1]. The annual total confirmed human cases has decreased substantially from 12,594 cases to 3429 cases between 2006 and 2012, and then resurged to 5399 in 2016 throughout the world. [Userpro_private]

JEV is endemic to China and Southeastern Asia. The case-fatality ratio  is approximately 30% among symptomatic patients, and over 35% in children. In the past, JEV transmission was only characterized in two paths: 1) reservoir–vector–reservoir, and 2) reservoir–vector–human. In 2016, scientists discovered the vector-free transmission of JEV from pig-to-pig [2], which seems to be a challenge to JEV control. Recently (in 2017), the first case of JEV transmission via blood transfusion has been found in Hong Kong (see [2]). This new finding indicates the possible JEV spread from human–to-human by passing through bloodstream. The new findings on the vector-free JEV transmission could have considerable impacts on public health planning.

JEV is an endemic disease in Hong Kong, and has been listed as the ‘mandatorily report disease’ since 2004. The city saw no local JEV human cases reported between 2006 and 2010, however, this was followed by a resurgence of cases since 2011. In our recent paper [3], we intended to study the scientific reason behind this phenomena.

 Why has there been a lull in JEV cases?

The ‘skip’ of JEV from 2006–2010 in Hong Kong was mainly due to the dramatic decrease of local farm pigs. Since JEV cannot spread from one human to another without mosquitoes, the decrease of reservoirs (farm pigs) played the most essential role in the lull of JEV. One possible reason of the JEV ‘resurgence’ since 2011 could be a new more ‘infectious’ JEV strain that invaded Hong Kong. If effective vector control could be implemented, JEV is likely to be eliminated locally.

 Why use a mathematical model?

Due to ethical issues, scientists have to avoid doing experiments under a number of situations, especially when studying diseases spreading dynamics on population level. A well-proposed (and biologically reasonable) modelling framework can offer us a chance to study the diseases transmission pattern from the theoretical side. Moreover, one of the powerful functions of a suitable mathematical model is the study numbers of ‘what if?’ question of interest. For example, what if the local mosquitoes are under control, say by a 50% reduction? How much would human infections reduce? Or, what if a proportion of local reservoirs (farm pigs) are effectively vaccinated?

By using the mathematical model, we studied the transmission pattern of JEV among mosquitoes, local farm pigs and humans on population level. We developed the transmission paths by referring to the biological and medical facts of JEV and we intended to study to what extend that local farm pigs are related to the JEV epidemics. It is also interesting to evaluate the effect of the vector-free transmission, and further look into the question that ‘can JEV persist among pigs without mosquito?’.

 What should readers take away from your report?

We propose the ‘skip’ of JEV from 2006–2010 in Hong Kong was mainly due to the dramatic decreasing of local farm pigs. The number of local farm pigs dropped from 350,000 to around 65,000 in 2006, which was the consequence of the local ‘pig rearing license surrendering’ policy. We successfully used the well-known concept of ‘critical community size’ (CCS) to explain the ‘skip-and- resurgence’ of JEV in Hong Kong. The CCS can be understood as the minimal population size in which a disease can persist indefinitely, in other words, in a population with size lower than the CCS the disease will die out.

The infection attack rate (IAR) is the proportion of the whole population infected during the epidemic. With the JEV, infection symptomatic ratio (of human) is from [0.48%, 0.81%], the IAR among pigs increased from [33.98%, 57.33%] to [56.10%, 94.67%] after invasion. Our study suggests the IAR (of pigs) could have been increased by the possible new JEV strain in Hong Kong as the estimated JEV force of infection among pigs increased 1.65-fold in 2010-–1. The estimated spill-over rate (from pigs to human) increased 6.5-fold in 2010–11.

Without vectors (mosquitoes), JEV is not likely to persist among pigs (with the basic reproduction number of pig-to-pig transmission path very close to zero). Therefore, vector control and prevention is an effective way to control JEV. Perhaps a larger proportion of JEV vaccine uptake among farm pigs could also be a way to reduce human infections.

 What recommendations do you have for future research as a result of this work?

Although monitoring JEV among pigs is very important, the reduction in local farm pigs did not lead to elimination of JEV in Hong Kong. Vector control and prevention of mosquito-bites remains the most important and effective measure in mitigating JEV outbreaks in Hong Kong. Vaccination before travelling to JEV endemic places is also recommended to prevent infection. Local disease surveillance organizations are suggested to pay attention to the possible new JEV strain(s) invasion that might have more aggressive infectivity.

References
  1. CDC. Japenese encephalitis. https://wwwnc.cdc.gov/travel/diseases/japanese-encephalitis
  2. South China Morning Post. Hong Kong tackles world’s first case of patient contracting Japanese encephalitis through blood transfusion. www.scmp.com/news/hong-kong/health-environment/article/2103667/hong-kong-tackles-worlds-first-case-patient
  3. Zhao S, Lou Y, Chiu A P, & He D. Modelling the Skip-and-resurgence of Japanese Encephalitis Epidemics in Hong Kong. J. Theor. Biol. 454, 1–10 (2018)
  4. Ricklin ME, García-Nicolás O, Brechbühl D, Python S, Zumkehr B, Nougairede A, Charrel RN, Posthaus H, Oevermann A, Summerfield A. Vector-free transmission and persistence of Japanese encephalitis virus in pigs. Nat. Comms. 7(10832) (2016)

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