West Nile Virus: Measures against Emergence in Malaysia

Introduction

West Nile virus has a potential to emerge in new areas and cause large epidemics as was witnessed in the United States following its introduction in 1999 [1]. The virus is now a global public health threat having been detected on every continent except Antarctica [2]. Once restricted to Africa where it was first isolated in 1937 [3], its expansion beyond its natural habitat and establishment in new areas is related to some viral, vectoral, anthropologic and environmental factors. These include viral adaptations, availability of competent hosts and mosquito vectors and suitable environmental conditions. The rapid spread through the United States was a surprise and a cause for concern; the virus had not been reported in the Western Hemisphere before 1999 [4]and despite efforts to control its spread, it successfully did spread through the country and spilled northwards into Canada and southwards to South America [5].

Historically, WN virus circulated in Africa, the Mediterranean, the Middle East and parts of Europe, causing sporadic outbreaks in humans and horses. Kunjin virus is a strain of the virus endemic to Australia was isolated in Malaysia in 1970 [6]. The outbreak in New York was caused by a strain nearly identical to the one that caused an outbreak in Israel previously [7]. The means of its introduction is unknown and shows how easy an infectious agent from a distant area can get introduced and become well adapted to local conditions elsewhere. In Malaysia, reports of WN virus activity was first published in 1963 and later in 1970 [6, 8]. More recently antibodies were detected in sera from captive birds in Selangor and from the Orang Asli population Open Access Journal of Veterinary Science & Research

[9, 10]. These clearly provide evidence of WN presence in Malaysia, though no clinic infections have been attributed to it in either humans or animals. Considering the potential of the virus to mutate and become pathogenic to humans and animals [11], it is important to monitor virus activity and control its spread before it causes an epidemic.

WN virus is a zoonotic flavivirus that naturally circulates between birds and Culex mosquitoes [12]. It can infect and cause disease in humans and a number of vertebrate species; these are however considered dead- end incidental hosts since they are not capable of perpetuating virus transmission. The genome of WN virus is a single-stranded RNA 11kb in size with a single open reading frame [13]. Mosquitoes acquire the virus following a blood meal from viremic reservoir hosts, which are several species of birds. The virus then replicates in the gut epithelium and eventually disseminates in the mosquito and replicates in the salivary gland. During blood meal on susceptible hosts, virus-containing saliva is secreted by the mosquito to prevent clotting, leading to infection.

About 3-14 days after infection a mild febrile illness is observed in about 20% of infected individuals. In humans, about 1% of infected individuals develop severe encephalitis as a result of the virus crossing the blood- brain barrier. Symptoms include high fever, stupor, headache, coma, neck stiffness, disorientation, tremors, muscle weakness, convulsions and paralysis. Death may occur following these symptoms and treatment is supportive in both humans and horses. Vaccines are available for horses but non for humans. Vector control is very critical in the control of WN virus.

WN virus outbreaks are typically first noticed in animals before human infections are observed. Effective outbreak prevention and control measure will depend on rapid and accurate identification of illnesses due to the virus in sentinel animals and in patients. The abundance of both the vectors and reservoir host for WN virus in Malaysia is a challenge especially for preventing animal infections. Reducing the population of and exposure to the vectors are central to the success of any prevention and control strategy against WN virus.

WN virus transmission be can be interrupted by preventing or minimizing mosquito bites. This can be achieved by eliminating the vectors, reducing the vector population and by putting a barrier between mosquitoes and people. Understanding the life cycle and feeding behaviour of the Culex mosquito can help in designing effective vector control strategies including those directly targeted at the vector and others focused on the environment and human behaviour.

Transmission Cycle of West Nile Virus

WN virus naturally exists in a transmission cycle between birds and mosquitoes. Infected birds can have a high and sustained viremia compared to dead-end hosts like horses and humans. They are thought to be important in the introduction of the virus to new habitats, and the start of a WN virus epidemic is usually marked by death in birds.

Ornithophilic mosquitoes acquire the virus during blood meals on infected birds. The virus causes a persistent infection, replicating in the midgut epithelia and concentrating in the salivary glands, resulting in high virus titre in the saliva [14]. Susceptible hosts are infected by the mosquito’s saliva when they are fed on.

Between its transmission from the birds to mosquitoes and other hosts, the virus constantly mutates through antigenic drifts, resulting in a diverse viral population. Through this constant change in its genome conformation, novel strains that are pathogenic and fit for transmission emerge, leading to outbreaks [15, 16].

Life Cycle of WNV Vectors in Malaysia

The life cycle of mosquitos typically has four developmental stages; adult, eggs, larval and pupal stages and generally takes between 13-15 days to complete. Mosquitoes breed in aquatic environments, where the female adult mosquitos lay floating eggs on water, each laying from 100 to 500 eggs. Culex eggs are cigar shaped and are laid in clusters. Swamps, puddles of water, tree holes filled with rain water are suitable for mosquitoes to lay their eggs in their natural environment. Closer to humans, clogged up gutters, heaps of trash, disposed cans and old discarded tyres all collect water in them and provides suitable breeding grounds for mosquitoes.

The eggs hatch into aquatic larvae in a few days. The larvae are submerged just beneath the surface and breathe through specialised structures. They feed and grow rapidly, undergoing 4 different moults in 3-5 days before they shade their larval skin and metamorphose to a pupa. During the pupal stage which lasts a day or two, feeding stops and development into adult mosquitoes in completed. The adults break out of the pupal skin, dry off Open Access Journal of Veterinary Science & Research

its wings, waits for its exoskeleton to harden and then fly off to feed on nectar, juice or blood.

Public Enlightenment and Behavioural changes

Certain behaviours can determine the level of exposure to mosquito bites and possible transmission of the virus. Wearing protective clothing, eliminating breeding sites especially in flower pots, using insecticides in the home, clearing bushes around the home premises and the use of insecticide impregnated mosquito nets are behavioural changes that can be helpful in vector control and prevention of transmission. To achieve this, the public needs to be informed about the risks of the vectors and the benefits of the behavioural changes.

Current Mosquito Control Strategies and Challenges in Malaysia

Dengue virus, a flavivirus closely related to WN virus is endemic in Malaysia. A vector control programme targeting its mosquito vectors: Aedes aegypti and Aedes albopictus has been ongoing for years, applying a combination of measures including adult and larva control through use of chemicals, environmental management, house inspections and fogging [24]. The cost of this programme in 2010 was US$73.5, representing 0.03% of the GDP for that year with a significant amount of directed at killing adult mosquitoes [25]. A full evaluation of this control programmes needs to be carried out to determine its effectiveness at reducing mosquito populations. Although the vectors for Dengue and WN viruses are different and both mosquito species have different ecological preferences and feeding behaviours, measures aimed at eliminating a particular species of mosquitoes may be beneficial in controlling more than just the target species, since insecticides will kill all mosquitoes, available breeding sites will be reduced for al species, and behavioural adjustments and practices would mean a reduction in contact with the vectors. However, this isn’t always true as a study in Macau showed that a decline in the population of Anopheles mosquitoes was followed by an increase in the population of Culex species [26]. A similar study on the effects of Aedes control on Culex population dynamics in Malaysia will be beneficial in implementing an integrated mosquito control programme. Concerns about the emergence of resistance to pesticides and the overall environmental impact of fogging needs to be investigated.

Recommendations and Conclusion

Available information suggests the presence and possible circulation of at least one strain of WN virus in mosquitoes, and antibody detection in birds and humans indicates exposure to the virus. Preventing an outbreak requires a well-designed strategy aimed at assessing the real risk of infection in livestock and humans and the control of vector population as well as preventing or minimizing contact between humans and the vectors. This can be achieved through strong cooperation between stake holders in human and veterinary health sectors, policy makers and the community.

Novel methods of vector control including the use of genetically modified mosquitoes that produce sterile progeny should be considered. This will eliminate the concerns about resistance to available pesticides and the environmental impact of using pesticide use.

An integrated mosquito surveillance and control system will provide information on mosquito populations, ecology and pathogens they harbour. This is essential for early detection and timely response to prevent an epidemic.