JEV We discuss mosquito vectors and models with respect to a subgroup of the mosquito-borne

flaviviruses. Falvivirus are very small and composed of a positive single-strand RNA and can cause

Encephalitis

JEV serocomplex within the Flavivirus genus contains several zoonotic sources of encephalitis

Wild wading birds (such as herons or bitterns) are the primary amplifying hosts, although over 91 bird species are known to be hosts of JEV. In urban areas swine are the dominant reservoirs.

The primary vector of JEV is the mosquito species Culex tritaeniorhynchus, but secondary vectors of JEV include Culex gelidus, Culex fuscocephala, and Culex annulirostris. Rice fields are the most favorable locations.

Three different vaccines for JEV are in use

It has the potential to quickly cross large distances as it can infect migratory birds

WNV infection was found in more than 61 species of mosquitoes as well as numerous other arthropod species such as ticks- primary vector are of Culex genus, different species in different areas of the world. In North America, transmission is highest in agricultural and urban habitats

Usutu Virus (USUV) is first found in USA but became famous after invasion in Europe through Austria, where it reached mostly by birds

In 2009, USUV first demonstrated pathogenicity in humans with neuro invasive infections in Italy and apart from bird, it has been isolated from both Culex and Aedes mosquito species

Murray Valley Encephalitis first discovered in Australia. The main amplifying hosts are birds, while the main vector is Culex annulirostris

The major encephalitic virus in the Americas, St. Louis Encephalitis. Birds serve as the primary reservoir and Culex mosquitoes as transmission vectors

Culex genus and the Aedes genus are of concern for the JEV viruses, although Culex much more so. From rural and wild landscapes in Asia to the heart of Chicago, Culex species are found around the world.

Culex species have been characterized through their distributions, genetic relationships, abilities to overwinter viruses, host preferences, mating behaviors, and virus competencies

Aedes mosquitoes are primary vectors of several of the mosquito-borne flaviviruses including dengue and yellow fever

Aedes aegypti is not known as a vector for any virus of the JEV serocomplex, yet one study has shown that Aedes aegypti, once infected, are capable of transmitting WNV through their bite

Asian Tiger mosquito, Aedes albopictus is competent for at least 22 arboviruses, including WNV and USUV

Aedes albopictus in its success as a rural maintenance vector of arboviruses is able to replace populations of Aedes aegypti in all but urban environments and susceptible to WNV more than Culex pipiens.

Model Types Mosquito population models fall broadly into two categories, deterministic and stochastic

Stochastic models usually produce ranges for each output and require more computational resources than comparable deterministic models. In general, stochastic models can more realistically represent real processes than deterministic models

Deterministic, mechanistic models generally use a set of differential equations to describe realistic processes evolving through time

The growth stages can be modeled with compartments, where a mosquito advances from one compartment to the next

Basic Reproductive Ratio and Equilibrium analysis to predict the possibility of Epidemic

Deterministic models are analytical and One advantage of the analytical nature of some of these models is their suitability for optimization. This feature permits mathematically optimal solutions for the control of vectors and disease outbreaks

Stochastic models are used to capture Uncertainty in model parameters and internal processes.

They use difference equations instead of DE. Mosquito movements can be described as exponential stochastic processes.

Computations are very complex in stochastic models than their deterministic counterparts. But extra care should be taken to avoid unrealistic outcomes when using deterministic models.

maturation rates, biting rates, egg-laying rates, extrinsic incubation period, mortality, and virus transmission efficiencies are important parameters to be modeled

They depend on temperature, vegetation, and rainfall

When the model includes a mosquito-borne virus, sub-models of all hosts with relevant demographic and disease parameters and the vector-host interactions should be added

As the mosquito life cycle is fast enough compared to host, the host portion of the model becomes irrelevant.

Among the 15 basic assumptions on RM model, only 3-5 are differed in last 40 years.

Past, Present, and Future of Japanese Encephalitis

Japanese encephalitis (JE) is a vector-borne viral disease that occurs in South Asia, Southeast Asia, East Asia, and the Pacific

Caused by zoophilic mosquito species as Culex tritaeniorrhynchus and gelidus

Though main reservoir is waddling birds, they spills over pigs and domestic animal as well as human.

JEV mainly occurs in epidemics

JE is found both in temperate and tropical regions

JE was likely introduced into northern Australia by windblown mosquitoes from Papua New Guinea

Main control is live attenuated vaccine that is costly

Vaccination pig a good way, but they are not effective in baby pigs because of the maternal antibody

Environmental management for alternative drying and wetting can reduce their breeding as well as increase rice yields

Chemical control plays a marginal role in JE control. During the period of high mosquito density spraying can break transmission cycle

Genetic studies suggest that JEV originated from an ancestral virus in the area of the Malay Archipelago

JE appeared as recurring encephalitis outbreaks in the summer season

Nearly half of the human population currently lives in countries where JEV occurs

In places where control measures such as vaccination, clinic are not in place JE is increasing and other places they are declining or stable.

The situation in North Korea, Myanmar, Pakistan, and Papua New Guinea remains largely unknown

The emergence of JE can probably be explained by 2 factors. First, JE-endemic countries experienced an unprecedented population growth in recent decades and Second, pig rearing has grown exponentially and rice-production systems, particularly irrigated rice farming, have increased both in cropping area and cropping intensity.

Pig production is doubled in China in 15 years and rice production is increased by 22% in 40 years

People living near irrigated rice fields are potentially at increased risk of infection

Largest irrigated rice area is India, followed by China, Bangladesh and Thailand

Pig production is reduced in Malaysia, North Korea and Japan

If rice cultivation and pig production are both present then the force of infection will be very stronger

Discovered 125 years ago, JE has spread widely in the 20th century even though vaccine are being used

High-quality data on transmission and incidence of JE are lacking in various countries

countries with successful JE control programs are Japan and South Korea

The following key control strategies and developments might explain the successful decline of JE in these countries:

1) large-scale immunization programs for humans,

2) pig immunization and the separation of pig rearing from human settlements,

3) changes in agricultural practices (e.g., enhanced mechanization and decrease of irrigated land)

4) improved living standards (e.g., better housing and urbanization)

JE incidence is increasing mainly in low income countries because of the paucity of JE immunization programs

Cambodia, Laos, and Myanmar, severe JE outbreaks could occur in the near future because of the increased pig farming and rice cultivation.

Muslim countries such as Bangladesh and Pakistan have traditionally been JE free but they are poor and highly populated and have high rice cultivation. So they are in the risk zone.

The overall trend of JE has been declining over the past 3 decades, and we anticipate that this trend will continue in the long term

Incidence of JE is coincident with the economic growth, as vaccination levels increase with it. But privatization of market based economy has adverse effect on it.

The incidence of JE in India is still increasing as there is no vaccination program

High coverage of vaccination among children increases the average age of infection of JE in Taiwan

Climate change has been implicated in the increase of transmission of several vector-borne diseases

Flooding will have serious effect on JE as that will change the pattern in agricultural practices

Climate change will also have effect on bird migration pattern which will in turn inflict changes in JE invasion

Virus spills over from reservoir to human during a dramatic buildup of Culex spp. That is due to extreme weather conditions.

JE can be controlled, with effective surveillance systems and vaccines playing key roles

Overview: Japanese encephalitis Japanese encephalitis is prevalent throughout Eastern and Southern Asia and the Pacific Rim.

Humans are accidentally infected and are a dead end host because of low level and transient viremia.

Japanese encephalitis was recognized in horses and humans as early as 1871

In 1924 a severe epidemic was reported from Japan

Mosquito transmission of JEV was suspected in the early 1930s and JEV was isolated from culex Tritaeniorrhynchus by Mitamura and his colleagues

The Japanese encephalitis serological group of flaviviruses includes 8 virus species and 2 subtype viruses with a geographical range encompassing all continents except Antarctica

The most members of flaviviridae genus are arthropod borne or ARBO viruses, a term that describes their requirement for a blood sucking arthropod to complete their life cycle.

The flaviviridae genus comprises more than 70 viruses, 40 of which are mosquito borne, 16 tick borne and 18 have no known vector

Spread of the disease: 1924- Japan, 1954- China, 1990- India

Although JE is primarily concentrated in Southeast Asia, 3 epidemiological regions have been identified

Endemic Region

Intermediary Subtropical Region

Temperate epidemic Region

Three possible mechanisms for transmission of JE has been suggested:

1. Wind-blown mosquitoes

2. Bird migration

3. Movement and transportation of infected host.

JEV is transmitted through a zoonotic cycle between mosquitoes, pigs and water birds. Humans do not participate in spread of JE of low level and short lived viremia.

Vertical transmission of JEV has been reported in 3 strains of C tritaeniorrhynchus, C. Pipiens, Aedes Albopictus, A. togoi, C. annulus, C. quinquefasciatus and Armigeres subalbatus mosquitoes

The domestic animals can get infected but show no evidence of viremia

Amphibians, reptiles and bats can become infected

Pigs are most important reservoir because if gets infected easily and stay infected for 2-4 days, long enough to transmit to mosquitos

Bird mosquito cycle is very important in maintaining and transmitting infection

Rainy season is the high time as the mosquito density is high

Two epidemics, during April to July (severe) and during September to December (milder), have been reported from Karnataka, India

JE virus can overwinter with hibernating mosquitoes both in adult and larvae phase.

The migrating birds in southern areas may reintroduce JE in temperate zones during summer

The role of snakes and frogs in overwintering of JEV has been suggested from Korea

JE is a disease of children (3 to 6 years) in the endemic areas. The age specific infection reduced after 14. However, it affects both adults and children in newly affected areas

The estimated ratio of symptomatic to asymptomatic infection varies from 1 in 25 to 1 in 1000

This variation depends on many factors such as viral factors, host factors and endemicity

About 10% of the susceptible population is affected each year

The incubation period of JEV is 5–15 days

A percent of patients has seizures, mostly children

Acute flaccid weakness in JE has been reported in 5–20% patients

Movement disorders are common in JE and have been reported in up to 60% of patients

After the bite of an infected mosquito, the virus amplifies peripherally producing transient viremia before entering into the central nervous system. The sites of peripheral amplification are dermal tissue and then lymph nodes. The mechanism of entry of JEV across the blood brain barrier is not known

Using real time polymerase chain reaction (PCR) studies in rat, JE virus RNA copies were found to localize in thalamus, striatum, brainstem and cerebral cortex by day 6 and were undetectable by day 20

The Spatial Heterogeneity between JapaneseEncephalitis Incidence Distribution and Environmental

Variables in Nepal Infection results in case fatalities of 0.3% to 60%

Major environmental drivers capable of amplifying JEV transmission are temperature and precipitation

The transmission season in Nepal starts from June to October with a peak in August

Vaccination and surveillance are used for reducing epidemics JEV.

Phylogeography of Japanese Encephalitis Virus:Genotype Is Associated with Climate

The circulation of vector-borne zoonotic viruses is largely determined by the overlap in the geographical distributions of virus-competent vectors and reservoir hosts.

Phylogenetic studies have divided JEV into five genotypes. They are typed basically depending on the locations they are found. In recent years, GI has displaced GIII as the dominant JEV genotype and GV has re-emerged after almost 60 years of undetected virus circulation.

Authors demonstrated that GIII and the recently emerged GI-b are temperate genotypes likely maintained year-round in northern latitudes, while GI-a and GII are tropical genotypes likely maintained primarily through mosquito-avian and mosquito-swine transmission cycles.

Ecology and GeographicalExpansion of Japanese

Encephalitis Virus Control of JEV is achieved through human and/or swine vaccination, changes in animal

husbandry, mosquito control, or a combination of these strategies.

Typically, there are two suspected 4-day amplification cycles in pigs, with the initial cycle infecting approximately 20% of pigs, which usually develop antibodies by day 10 post infection. This second phase of viral amplification results in up to 100% porcine seroconversion.

Mosquitoes become infected by feeding on viremic pigs and, after a 7- to 14-day extrinsic incubation period (EIP), transmit the virus to other susceptible pigs.

No human cases were detected in areas where porcine asynchronous seroconversion occurred

two epidemiological patterns of JEV have been recognized: endemic activity in tropical regions, such as southern Thailand and epidemic activity in temperate and subtropical regions

The only geographic area where all genotypes are found is the Indonesia-Malaysia region

The EIP was temperature dependent and ranged from 6 days post infection at 28◦C to 20 days at 20◦C (126).

Cx. Tritaeniorhynchus eats readily on pigs even though they are mostly attracted to cattle

Humans account for only a small proportion (less than 5%) of blood meals for most Culex vectors of JEV in Asia.

Reintroduction:

Overwintering

Introduction by Migrating Birds, Bats, or Mosquitoes

Prevention and Control:

Vaccination

Control Measures Targeting Vertebrate

Mosquito Control

JEV has reached Australia, but not able to start an epidemic. Possible reasons for this include

(a) the presence of related flaviviruses that may provide cross-protection against JEV infection in susceptible hosts

(b) Cx. Annulirostris may have different vector competence to the different genotypes of JEV

(c) an inclination for Cx. Annulirostris to feed on marsupials and not pigs or wading birds

There is the potential for JEV to spread to the Americas, Europe, or Africa, but the long distance from endemic areas makes this difficult, and modern pig husbandry may impede virus amplification.

Review of Climate, Landscape, and Viral Genetics as Drivers of the Japanese

Encephalitis Virus Ecology Although five JEV genotypes circulate, neither clear-cut genotype-phenotype relationship nor clear variations in genotype fitness to hosts or vectors have been identified.

Density, size, spatial arrangement of landscape either facilitate or impede or impede the movement of vectors

JE infections are lethal in about 25–30% of cases, mostly in infants, and lead to permanent sequelae in about 50% of cases.

An effective vaccine developed in 1941, but still there are cases of JEV and now almost three billions of people live under the JE-endemic countries

Five JEV genotypes have been distinguished by nucleotide sequencing of capsid, precursor membrane, and envelope genes

Among them five the first three are restricted to Asia, while the fourth is in Eastern Indonesia. The fifth is largely abundant in Malaysia

The genotypes can transfer from one to another in depending on the spatial location.

Vaccines are only derived from genotype III strains

Over 30 mosquito species (family Culicidae) belonging to the Aedes, Anopheles, Armigeres, Culex, and Mansonia genera are recognized to potentially carry JEV

Not all the mosquito species are equally susceptible to infection. Variations of competence may be due to differences in the susceptibility to infection of mosquito midgut and salivary gland

There is two cycle of infection. They are:

Bird-Associated Wild Cycle

Pig-Associated Rural Domestic Cycle: The intensity of circulation in farms depends on the amount of pigs reared by farm, their age at slaughter, their reproduction rate, and the vaccination effort

Cx. quinquefasciatus is another potential vector of the JEV domestic cycle for it’s domestic water collection and use of wastewater from pig farms for breeding

The introduction and reintroduction of vector-borne and zoonotic diseases as well as variations in disease risk and incidence are strongly driven by environmental factors

The most important factors are climate, land cover and land use

Rainfall and temperature are the most important climactic factors as they directly control vector density

Vaccination is the most effective way to reduce the incidence of JE in humans, yet it has no effect on the JEV transmission cycle

pigs represent a relevant sentinel model, the surveillance of which could predict a potential JE outbreak in a human population nearby