Abstract. Dengue is transmitted to human through mosqui

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AbstractDengue is transmitted to human through mosquito bites which makes it a vector-borne disease. Itis believed to be one of the most significant tropical and sub-tropical diseases, but because ofurbanization, climate change, and international traveling, it is found to be scattered all over theworld. Hence, it is necessarily required to control the scattering of Dengue virus and treatment ofdiseases caused by Dengue is also required. Dengue virus has to identify the cell surfacereceptors of the host with the help of virus-encoded protein envelope in order to infect the host.Therefore, recognition of virus receptor is very significant to understand the process of infectionand in developing the anti-virals and vaccines. However, enough knowledge about Denguereceptors in human hosts and insects is not available. Characterization of all the assumed Denguereceptors has been done poorly. The project is aimed at identifying and characterizing theauthentic Dengue receptor with the help of various stringent cellular and molecular techniques.We have become successful in knocking out a putative Dengue receptor from the cell line ofmosquito by using a state-of-the art tool used for genome editing known as CRISPR. This is avery simple yet powerful and versatile tool used to silence certain genes present in the genome.CRISPR/Cas9 system in bacteria/Archaea was developed as a defense mechanism to fight phage(virus) infections. Nowadays, it is used as a tool to edit gene in numerous organisms for thewhole lifetime.Dengue Fever:Dengue is an RNA virus that is single-stranded belonging to the genus of Flavivirus and to thefamily of Flaviviridae. In recent years, this mosquito-borne viral disease has spread rapidly inevery region of WHO. Transmission of dengue virus is mainly through female mosquitoes fromthe species of Aedes aegypti and Ae. Ablopictus to a lesser extent. Infections such as yellowfever, chikungunya, and Zika are also transmitted by the same mosquito. Local variations such astemperature, rainfall, and unplanned rapid urbanization results in the widespread of Dengue inoverall tropics.During Thailand and Philippines Dengue epidemics in the 1950s, first severe Dengue (DengueHaemorrhagic Fever) was recognized. At present, severe Dengue has become the chief cause ofhospitalization and death among the affected adults and children in the regions of Latin Americaand Asia.Dengue is caused by four closely related distinct serotypes of virus (DEN-1, DEN-2, DEN-3, andDEN-4). Recovery from the infection caused by one serotype ensures lifelong immunity againstthat particular serotype and partial or temporary cross-immunity against other serotypes.Following infections caused by other serotypes intensifies the risk of causing severe dengue.Lifecycle:Dengue virus is continuing its existence in urban lifecycle because it is being transferred frommosquito to humans and then back to mosquito from the human. Aedes aegypti mosquito is theprimary vector of Dengue virus. However, Aedes albopictus may also transmit the virus (Brooks,Carroll, Butel, Morse, & Mietzner, 2010). Female mosquito feeding on viremic human results in
the transmission of Dengue virus from human to mosquito. The period of development lasts 8-12days within the mosquito, and it comprises of a systematic spread of the virus from the mid-gut.Once this period is over, the transmission of the virus to any human can again take place at anypoint of mosquito's remaining life (WHO, TDR, 2009).Global burden of dengue:A radical growth in the global incidence of dengue has been recorded in the recent decades. Theactual number of cases of dengue either remains underreported and misclassified. As per a recentestimate, there are 390 million per year infections of dengue (95% reliable, in the interval of284–528 million) out of which 96 million (67-136 million) are observed clinically (with somedisease severity). 1 Another study about the existence of the virus suggests that 3.9 billion peoplefrom 128 countries have the threat of being infected by dengue virus. 2 The number of cases was2.2 million in 2010 and increased to 3.2 million in 2015 as reported by those members from 3WHO regions who report their annual number of cases on a regular basis. Although the totalburden of the disease all over the world is still uncertain, the activities commenced recording allthe cases of dengue partially describes the steep increment in the number of testified cases in thecurrent years.Other symptoms of the disease include its patterns that are epidemiological that include hyper-endemicity in various serotypes of dengue virus in various countries. Frightening effects onhuman health and national and global economies.Severe epidemics of dengue was experienced by 9 countries before 1970. The prevalence of thedisease is found to be present in 100 or more countries from the WHO regions of the America,Africa, the Eastern Mediterranean, the Western Pacific, and South-East Asia. South-East Asia,America, and Western Pacific regions being affected most seriously.Over 1.2 million in 2008 and more than 3.2 million in 2015 cases across Americas, WesternPacific and South-East Asia were recorded (As per the official data recorded by member states).The number of cases in the record is noticed to be increasing recently. In America alone, therewere 2.35 million reported cases in 2015, out of which 10 200 cases were treated as severedengue which resulted in 1181 deaths.The spread of the disease is not only increasing the number of cases, but it is resulting in theoccurrence of explosive outbreaks. Europe is now experiencing the threat of possible denguefever outbreak as the first case of local transmission was reported in Croatia and France and 3imported cases in some other European countries. In the year 2012, more than 2000 casesreported as a result of dengue outbreak on Madeira Islands of Portugal, and there were importedcases in the mainland of Portugal and 10 other nations of Europe. After malaria, dengue is foundto be the second most diagnosed reason of fever among the travelers coming back from middleand low-income nations.Cases were recorded in Yunnan province of China and Florida (United States of America) in theyear 2013. Some of the South American countries such as Costa Rica, Mexico, and Honduras arecontinuously being affected by Dengue. In Asia, the increase in cases of dengue after a gap of
some years was reported by Singapore and Laos has also suffered the outbreaks. As per theindications from the trends a rise in the number of cases in the Cook Islands, People’s Republicof China, Malaysia, Fiji, and Vanuatu in 2014. The same year, Pacific Island countries were alsoaffected by Dengue Type 3 (DEN 3) after a gap of 10 years. Japan recorded the occurrence ofDengue after the gap of 70 years.In 2015, with more than 15000 cases in Delhi, India, was recorded as its worst outbreak after2006. An outbreak of 181 cases was reported in The Hawaii Island, United States of America, in2015 and the transmission continued in 2016. The countries of Pacific island such as Tonga, Fiji,and French Polynesia continued to record cases. Large dengue outbreaks were recordedthroughout the world that characterized the year 2016. Over 2.38 million cases in some regionsof the America were recorded in 2016, out of which Brazil alone added nearly 1.5 million cases,which was about 3 times higher than those recorded in 2014 where there were 1032 denguedeaths in the same region. Over 375 000 dengue cases were suspected in the Western PacificRegion in 2016, of which 176 411 cases were reported in the Philippines and 100 028 cases inMalaysia, both the countries demonstrated the similar condition in the previous year. Anoutbreak of over 7000 suspected cases was declared in the Solomon Islands. In Burkina Faso,Africa, a localized outbreak of 1061 probable cases of dengue was reported.In 2017 (as per Epidemiological Week 11), 50 172 dengue fever cases were recorded in theRegion of America, a decline when compared with those in previous years. Some Member Statesof the Western Pacific region recorded dengue outbreaks and DENV-1 and DENV-2 serotypescirculation.Transmission:The mosquito Aedes aegypti acts as a primary vector for spreading dengue. The transmission ofvirus takes place from the bites of infected female mosquitoes to human. Once the virusincubation period of 4–10 days get over, an infected mosquito can transmit the virus for itsremaining life. Symptomatic or asymptomatic infected humans are the primary carriers andresult in multiplying the virus because for uninfected mosquitoes, they serve as the source for thevirus. Already infected dengue virus patients are capable of transmitting the infection (for 4–5days; maximum 12) through Aedes mosquitoes after the first appearance of symptoms. Urbanhabitats serve as the livelihoods for Aedes aegypti mosquitoes and man-made containers as theirbreeding grounds. Ae. aegypti feeds in day-time unlike other mosquitoes; early morning andevening before the dusk are the peak times when its biting is most likely to occur. Multiplepeople are bitten by female Aedes aegypti in each of its feeding periods. Aedes albopictus, whichis considered the secondary vector of dengue in Asia, has been spread to North America and over25 countries of European Region, primarily through trading the used tires and other goods whichact as a breeding habitat (e.g. lucky bamboo) internationally. Aedes albopictus is very adaptivewhich helps it to endure in Europe where regions are cooler temperate. Its adaptation to thetemperatures below freezing, the ability to shelter in microhabitats, and hibernation are the maincauses of its widespread.Manifestations:
Infections from Dengue virus can be manifested in different ways. Infected persons may beasymptomatic, or dengue hemorrhagic fever with or without shock syndrome of dengue (Table1), or may have manifestations corresponding to that of typical dengue fever. WHO has dividedthe dengue illness course into 3 stages: febrile, critical, and recovery. Once 4-10 days ofincubation period are over, the dengue fever is said to be at the beginning of the febrile phase.Patients suffer sudden inception of high-grade fever, and frequently patients suffer headaches,myalgias, retro-orbital pain, arthralgias, and facial flushing. Many complain of vomiting, nausea,and appetite loss. Injected pharynx, sore throat, and conjunctivitis are sometimes noted. Therecan be minor hemorrhagic manifestations such as petechiae, gingival and epistaxis bleeding andrare bleeding in gastro intestine and vagina. At this time, a person can suffer from hepatomegalyand a consistent decline in the count of white blood cells. This febrile phase lasts 2-7 days, and atthis stage, it is very difficult to determine which of the cases will end up severe dengue fever(WHO, 1997; WHO, TDR, 2009).The critical phase starts from 3 to 7 days, the temperature declines to 37.5-38°C or less andremains fixed. At this time, there can be a growth in capillary permeability resulting in a rise inhematocrit (WHO, TDR, 2009). Growth in plasma leakage and capillary permeability is assumedas dengue hemorrhagic fever (WHO, 1997). It is worth noting that before the occurrence ofplasma leakage, consistent decline in the total count of WBCs and a rapid decline in the count ofplatelets. If capillary permeability increases, the condition of the patient improves and isassumed to suffer from dengue infection of non-severe type. The manifestation of anyone of thefollowing is considered to be severe dengue: leakage of plasma with or without shock, severeorgan impairment, or severe bleeding (WHO, TDR, 2009). An abdominal ultrasound or a chestX-ray can be used in recognizing severe dengue cases, as increased capillary permeability maylead to the development of ascites and pleural effusion (WHO, TDr, 2009). As verified byhematocrit elevation hemoconcentration will occur, In addition to leucopenia andthrombocytopenia shown by labs (WHO, 1997).Leakage of excessive amounts of plasma in the extravascular space leads to the occurrence ofdengue shock syndrome. This normally occurs around day 4-5 or when the fever decreases(WHO, TDR, 2009). Patients will show symptoms of circulatory failure such as blotchy, cool,and edematous skin, tachycardia, circumoral cyanosis, a narrowing pulse pressure, and weakpulse (WHO, 1997). It is significant to note that there is a rise in diastolic blood pressure whilesystolic blood pressure does not change. This can be ignored if systolic blood pressure remains inthe normal range. Though the narrowing pulse pressure is a negative symptom of shock and thepatient needs quick and ample care. Pulse pressure lesser than or equal to 20mm Hg is defined asthe shock (WHO, TDR, 2009). Treatment of shock results in recovery in 2-3 days (WHO, 1997).Multiple organ failure, disseminated intravascular coagulation, and metabolic acidosis are likelyto occur if the identification of shock does not take place and aggressive treatment is not given.Severe hemorrhages and occurrence of death happen at last (WHO, TDR, 2009).If appropriate management and monitoring is done, the recovery phase that consists ofextravascular fluid reabsorption starts within 48-72 hours. Improved symptoms show that the
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