Sustainable Solution Against Dengue Kypros Christodoulou Biology Essay

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Dengue fever is an infection caused by the bite of the mosquito Aedes. This disease was discovered many years ago, but so far there is no vaccine to prevent disease. According to the World Health Organization (WHO), there are approximately 50 to 100 million cases reported each year and many tropical regions are suffering for dengue epidemics. Current approaches to reduce the population of the mosquito Aedes rely on biotechnological methods.The aim of all methods is to achieve sustainability. On this essay some of them are produced as well as a novel idea for discussion and experimentation.

Dengue viral infections, affects the tropical regions; and are considered to be one of the most severe diseases which is transmitted by arthropod vectors (Rigau-Perez et al., 1998), while it is estimated that in an annually basis 50-100 million cases of Dengue fever and 250 000 to 500 000 cases of Dengue haemorrhagic fever are reported . Additionally, it is observed that the disease continues to expand in endemic areas of South East Asia, Central and South America and other subtropical regions. (Whitehead et al., 2007).

Also, important to be mentioned is that the dengue viruses (DENV) are members of the Flavivirus genus,of the Flaviviridae family, a family where other dangerous viruses are included and could also posing threat to public health, e.g. yellow fever virus ,West Nile virus Japanese encephalitis virus and tick-borne encephalitis virus. (Whitehead et al.,2007)

Dengue viruses are consisted of four serotypes DENV-1, DENV-2, DENV3 and DENV-4 and are capable to cause all the possible clinical manifestations, ranging from an asymptomatic infection to dengue fever (DF) or even resulting to the most severe forms of the infection, the dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS).(Whitehead et al.,2007). At the beginning of the infection, patients are suffering from severe headaches and mild to high fever accompanied by muscle and joint

pains. However, a distinctive feature of dengue is the bright red rash that develops in the legs and chest. Also it is observed the decrease of the number of platelets and white blood cells.  In the case of dengue hemorrhagic fever, patients may have vomiting, blood loss or even loss of appetite. In cases where symptoms are severe or the rash is not visible, the patient may be misdiagnosed as flu or a common viral infection. But when the clinical examination is whether blood pressure is low and the patient has swollen glands and whether the neck and eyes look red, then dengue fever can be concluded. Unfortunately, there are not anti-viral or steroid treatments for dengue haemorrhagic fever. The patient should be given only paracetamol in cases of severe bleeding or a low platelet count, platelet transfusion is done. If diagnosed early, the infection will last for approximately 6 to 7 days. However, it is a misdiagnosis or delay in treatment can also lead to liver get affected or even worst to be fatal.(Mc Bride et al.,2000)

All the types of the DENV are transmitted to humans through the bite of an infected mosquito, called Aedes aegypti. The Aedes aegypti is a highly domesticated mosquito, and also the predominant vector of DENV. Moreover another Aedes species the Aedes albopictus can also sustain transmission.

The dramatic increase in the incidence of the DENV in the tropics it is strongly related with the geographical expansion of A aegypti caused after the poor efforts of vector control, as well as the urbanisation and the increase of the migrated population. Moreover DENV acts in an unusual way among the other arboviruses. This virus does not require an enzootic cycle for maintenance of epidemic transmission in humans. Rather, the virus is maintained by a human-to-mosquito-to-human cycle of transmission. (Whitehead et al., 2007).

As already mentioned there is no antiviral for treatment, although efforts are been trying on this field by some pharmaceutical companies, in order to create an effective vaccine. Nevertheless, it is not an immediate priority the creation of an effective, safe and affordable vaccine. (Whitehead et al., 2007)

At present the only efforts to decrease the dengue transmission are attempts to reduce the mosquito population, which might seem to be a simple matter of the treatment or elimination of infested containers but is not. Although every campaign started in order to achieve the reduction was very, but the problem was that is was hard to continue, because they require discipline and diligence. Great importance was also given in the usage of insecticides, firstly to organochloride insecticides and after to organo-phosphorus larvicides, as well as aerosols targeted at adult mosquitoes and mainly used outdoors as ultra-low volume (ULV) concentrations. Aerosols are mainly used for emergency situations like when it is appropriate the control during epidemic transmission as part of an integrated vector elimination effort, including environmental management, source reduction, and larvicides. Although, because it is easy to be used, was established as the principal response even before and after dengue epidemics has become widespread and unfortunately was the worst treatment, because ULV aerosols have very limited impact on adult female Ae aegypti and no impact at all on the immature stages. As a result no sustainability was achieved and the problem was still remained. (Rigau-Perez et al., 1998),

More recently, scientists understood that they need drastic solutions in order to achieve sustainability, and researchers are testing new approaches, in order to suggest the appropriate one. Current approaches rely on the contribution of biotechnology. One approach is sterile insect technique (SIT). SIT was used for many years in the control of the population of specific agricultural pests. It is an environmental friendly approach and the Aedes aegypti might be a suitable target for suppression or local elimination through the method. This relies on the fact that Aedes aegypti already reared and manipulated in the laboratory, is also found suitable for mass rearing, and is found at relatively low densities in disease-endemic locales.(Fu et al .,2010) Although, there are not at present any large-scale SIT programs against Aedes mosquito or any other mosquito species, whilst the use of SIT against mosquitoes is consider to be problematic, because of the fitness costs and operational difficulty of irradiation, and the density-dependent nature of the target mosquito populations.(Fu et al.,2010) Additionally,on the SIT programms it is preferable the release of male insects, due to the fact that they do not bite as well as on the fact that the transmission of the viral is cause by adult females. Another potential problem is the distribution of mosquitoes, because adult mosquitoes are less robust and more likely to suffer damage during transit and release in contrast with other SIT target species, like Ceratitis capitata (Medfly) and Cochliomyia hominivorax (New World Screwworm). .(Fu et al .,2010)

Those potential problems could be overpass with transgenic insects carrying specific novel traits, including conditional genetic sterilization or lethality that removes the need for irradiation. .(Fu et al .,2010) Transgenic insects carrying a female-specific lethal gene can be used to remove females prior to release. "A system based on a lethal gene (release of insects carrying a dominant lethal (RIDL)) that acts late in development can inhibit the develop of the mosquitoes from becoming adults, allowing them to survive and compete at the larval stage, when density-dependent competition occurs. On this model system it is expected that fewer male mosquitoes of a late-lethal strain need to be released as compared to those carrying an early-lethal gene or irradiated strain to achieve an equivalent level of control of a target population." (Fu et al.,2010)

Another research approach is the possible use of RNA interference in order to develop dengue virus resistance in genetically modified Aedes Aegypti. The possible strategy is to change vector populations competent to transmit DENVs with pathogen incompetent vectors . What is necessary to be done is the identification of the proper genes expressing antiviral molecules in the vector, attach those genes to a genetic drive system (transposable elements (TE), meiotic drive, or homing endonuclease genes) and introgress the gene(s) into field populations.(Travanty et al.,2004)

Moreover the endosymbiotic bacterium Wolbachia is another potential vehicle that can be used as a way to drive transgenes into insect vector populations for disease prevention. Wolbachia are intracellular, maternally inherited bacteria that influence the reproduction of insects via cytoplasmatic incompatibility (CI). Due to the effects of CI, a Wolbachia-uninfected female will not breed with infected males, thus the frequency of uninfected individuals will be reduced and the frequency of the Wolbachia-infected insects will be increased in the population and therefore, other maternally inherited transformed symbionts would be spread within an insect population in association with Wolbachia , increasing the frequency of the

transformed symbiont. This mechanism has been observed in Ae. Aegypti. (Rasgon et al.,2004)

Finally a proposed method that it would be a good hypothesis for discussion as well as experimentation; would be an engineered insect with a dual suicide control system. Two genes to be used on this operational system. The one suicide gene will targeted against the transgenic mosquitoes, where the suicide gene will be activated when the dengue virus will entry into the cell causing the suicide of the infected mosquito; and the other suicide gene will have as a target the wild type mosquitoes. Both of them will be expressed in the transgenic species. The system will be work with two different proteins the one will be the suicide protein, while the other will be the anti-suicide receptor which is modified for a wild type receptor. The suicide protein binds either to wild type or anti-suicide receptors. If the suicide protein binds the wild type, it causes suicide while if it binds the anti-suicide receptor, the protein is will not work. As a consequence when the wild type mosquitoes come into contact with transgenic mosquitoes will die. For this project they will be engineered and males and female insects so as to achieve the release of transformed eggs into the environment. Both males and females are transformed. The eggs of transformed mosquitoes will be released into the environment. When they will be ready to mate they will have two options. The transgenic female will have two options of mating, either with a transgenic male or a wild type male. So if a transgenic mosquito mates with a wild type, then it will be allowed the transcription and translation of suicide gene leading to death of the wild type. This system will allow the transgenic mosquitoes to be established at the domestic population and will also prevents the increase of the infected mosquitoes, thus it is a drastic biocontrol solution and therefore a solution that does not harm the environment.

In conclusion, Dengue is one of the most serious viral infections, which has no vaccine to prevent it. A bite from the Aedes mosquito can cause the infection. A way to prevent infection is the reduction of the mosquitoes.Scientists are looking for a sustainable solution and most probably biotechnology will give the possible answer. The breeding of genetically modified mosquitoes will probably be the next attempt of the scientists in order to limit the spread of the infection.