An Overview Of The Dengue Virus Biology Essay

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Dengue is a disease caused by one of the dengue viruses (CDC, 2011), DENV-1, DENV-2, DENV-3 or DENV- 4 (Guzman, 2002). This virus can be transmitted to vulnerable host such as human by infected vector, female Aedes mosquito during blood-feed period. There are possibly two species of mosquitoes that transmits dengue. Both are from family of Flaviviridae, Aedes aegypti and Aedes albopictus (Robert & David, 2002).


The origin of dengue is not very clear. According to one of famous established website, Dengue Virus, Chinese medical encyclopedia from the Jin Dynasty is the first documentation of a dengue fever case that referred to a water poison associated with flying insects.

In one of the paper titled Dengue and Dengue Hemorrhagic Fever: It's History and Resurgence As a Global Public Health Problem by Gubler (1997), both DENV and its primary vector, the Aedes aegypti originated in either Africa or Asia continent. During the 17th, 18th and 19th centuries, Aedes aegypti migrate from Africa in water container on slave ships during African slave trade (Lee, 2004). However, due to long journey time, epidemics of disease were less reported. Numbers of tropical countries with active shipping ports experienced outbreak of dengue by 1800.

Probable cases of dengue epidemics that occurred simultaneously in Asia, Africa and North America was first reported on 1779 to 1800. In 1823, the word 'dinga' was used for the first time to portray dengue disease in Zanzibar. Thomas Lane Bancroft proposed that Aedes aegypti mosquito was responsible in dengue spread in 1906. In 1907, two scientists, Percy Ashburn and Charles Franklin Craig confirmed that 'filterable virus' is the causative agent of dengue, the second human viral infection after yellow fever.

In 1939-1945, during World War II, due to huge demographic transformation and ecological interruption in Asia region, including loads of suitable breeding habitats for mosquitoes, disruption supply of water, and surge in people mobility from rural urea to urban had led to outbreak of disease. Endemic of disease occurred in Southeast Asia and Pacific during the same period of WWII. On 1944-1945, isolation of many dengue strains by inoculating virus sera into volunteers was done by Albert and his colleagues.

In Malaysia, first case of DF was reported in 1902 by Skae, followed by DHF in 1962. Since then, many dengue epidemics are reported. Paper published by Skae titled Dengue Fever in Penang stated that first dengue outbreak that is in 1901 happened in Penang. Dengue has become endemic in Malaysia by 1960's and in 1962, the first laboratory-confirmed DHF case was reported in Penang. DENV was first isolated by Sabin and Schlesinger in 1944.

Type of dengue

Dengue can be classified based on case definition. In case definition classes, dengue can be categorized into three, which are classic dengue (undifferentiated fever), DHF and DSS. DHF can be further classified into grade I to grade IV (WHO, 2009). A few criteria need to be determined by health care professional before classified patient into that particular category.

In classic dengue, clinician must be able to identify symptom such as acute fever for two to seven days accompanied by two or more signs of retro-ocular pain, myalgias, arthralgias, rash, hemorrhagic manifestations or leucopenia. DHF is defined by more severe clinical manifestations, which is signs of haemorrhage and any evidence of vascular leakage such as positive tourniquet, test, petechiae, thrombocytopenia and so on that can lead to DSS and death. In DSS, patients may present criteria such as DHF in addition of circulatory failure than can be detected by rapid and/or weak pulse, cold skin and hypotension (Avila-Aguero et al, 2004).

According to WHO, DHF can be classified based on severity of cases. In grade I, symptom such as fever accompanied by unspecific symptoms may present plus evidence of hemorrhagic manifestation such as positive tourniquet test. In grade II, all sign stated in grade I in addition with spontaneous bleeding. Grade III and IV, DSS is diagnosed with patient in grade III present signs of


Dengue is caused by DENV that is transmitted through saliva of infected female Aedes mosquito that act as vector to human as a host. Two common species are Aedes aegypti and Aedes albopictus. DENV has four serotypes that circulating concomitantly, which is DENV-1 to DENV-4.

Viral serotypes

There are four serotypes that are related with DENV worldwide including in Malaysia, which are DEN-1 to DEN-4 (Guzman, 2002). According to Zamberi sekawi et al (2005), even though in the same season all the serotypes may concomitantly circulate, one of those serotypes appears to be predominating over other serotypes at one particular time. In Malaysia, if patient present symptoms such as high fever and rash, health care provider will treat symptoms as dengue until all the laboratory test or clinical progress come back negative. However, currently numbers of patients show unusual clinical manifestation such as symptoms related to central nervous symptoms. McMinn (1997) conclude that this may be due to the mutation of specific E protein gene along with other gene and non-coding region of ribonucleic acid (RNA).

From 1985 to 2004, DEN-4 had not showed dominance. From one of the study conducted that involving DEN-2, the DEN-2 strain had evolved from pre-existing DEN-2 gene pool for three decades make it dormant and this strain became predominant in the following cycle if it encounter favorable condition for it to mutate. Genetic recombination between different specific dengue serotypes is unavoidable since it may have dissimilar virulence characteristics and clinical manifestation. Dengue epidemic in Malaysia such as in years of 1993 to 1994 may results of globalization and ease of travel between countries that introduce new strains from foreign countries (Kobayashi et al,1999).


Figure 1: Transmission of dengue virus. Adapted from Dengue Fever Management Plan, 2000

Figure 2: Viral cycle in mosquito body. Adapted from

Dengue virus is transmitted by female Aedes mosquitoes. It circulates among host-Aedes mosquito-host cycle. Figure 1 show the cycle of virus transmission. DENV-infected female mosquito bites human and transmit dengue virus to human's blood. Figure 2 shows that the virus invasion in human's body system starts when dengue viruses enter the human body via the salivary gland of the mosquito during blood-feeding period of the mosquito. In mosquito itself, the DENV in the infected human blood that enter the mosquito will replicate in mosquito's organ(s) such as midgut, neural tissue and so on. Then, the viruses will enter body cavity of the mosquito that will finally migrate to salivary gland of the vector and the cycle repeated again.

In figure 3, in human, after DENV has been transmitted to blood circulation, human as a natural host will has period of viremia that last three to twelve days but in average, four to five days. However, during extrinsic incubation period, DENV can last eight to ten days. In this period, DENV will replicate in host and vector's organ(s) and in most cases, no significant sign has been reported in host. DENV infects white blood cells and lymphatic tissue and when it reach maturity, it will be released to the blood circulation and infect other organs. Cycle of DENV transmission will goes on when another uninfected female Aedes mosquito bites infected host and acquire DENV.

Figure 3: Incubation period of DENV in host. Adapted from


Number of dengue cases keeps increasing from years to years. From years 1999 to 2003, there are 6,577 cases of DF were reported in one of the government hospital, Hospital Tengku Ampuan Rahimah (HTAR), Klang with most of the cases occurs among male patients aged above 12 years old with 5,742 cases. Among all races, Malay population is most seriously affected (Jamaiah et al, 2005).

According to statistics of DF and DHF by Ministry of Health, there are increases in incidence rate per 100,000 populations. Table 1 shows that from year of 1999 until 2006, incidence rate of DF is increasing but in case of DHF, incidence rate is fluctuate but from 2003 to 2006, numbers are keeps rising.

Table 1: Incidence rate (per 100 000 population) of communicable diseases.

Adapted from MoH.


Dengue Fever

Dengue Haemorrhagic Fever

























Study on epidemiology and new initiatives in the prevention and control of dengue in Malaysia done on 2001 stated that the largest, 8.1 percents from 1,966,722 premises of Aedes breeding is factories followed by 6.8 percents is abandoned housing projects and the lowest is houses or shops that constitutes less than one percent. In dengue control programme that the chief purposes is to reduce the morbidity and mortality rate of DF/DHF, six aspects that are disease surveillance and control, vector surveillance and control, public education, inter-agency collaboration and community participation, quality assurance and research and training need to be covered. Eight strategies have been developed and one of them is public education through health education activities in the community and with community involvement because it require everyone effort from public to government in order to control this infectious disease (Ang & Singh, 2001).

Pathogenesis of DHF/DSS

After infected by DENV, body will start to response by producing one of classical symptoms of dengue during acute phase of infection, which is fever. Mediator, heat-inducible factors such as cytokines, will be circulating in blood and induce body thermal homeostasis (Leon, 2002).

In innate immune system theory, Lei et al (2001) and Noisakran & Perng (2008) propose hypothesis of DENV may trigger CD4/CD8 ratio inversion that interfere with the ability of body defense system to eradicate viral load but also results in excessively produced cytokine that will further lead to progressive damage of monocytes, endothelial cells and hepatocytes results in cell apoptosis. Hemorrhage mechanism is triggered by platelet destruction that takes place when body develops autoimmunity against platelet-specific antigen with the aid of dengue antibody-virus complex that binds to the HPA glycoprotein leads to cross-reactivity of anti-platelet antibodies (Soundravally, 2007).

According to Avirutnan et al (2008), complement system is responsible in pathogenesis of flavivirus infection. In CR3 expressed cells, activation of antibody-dependent complement might enhance viral infection. There is a theory that formulated that infected cells express DENV antigen on their cell surface that enhances formation of immune complex and deposition of complement (Mehlhop et al, 2007). Avirutnan et al again revealed that DENV NS1, one of the DENV's antigens might be responsible in complement activation but in further study done by the same researcher shown that DENV NS1 requires specific anti-NS1 antibodies for complement usage.

Laboratory investigations

Disease monitoring laboratory tests

When a patient is admitted or seek for medical attention, clinician will order laboratory to conduct full blood count (FBC) and Liver Function Test (LFT).

In FBC, assay of White cell count (WCC), Haematocrit (HCT), and Thrombocytopenia will be done (CPG, 2010). In WCC, as increase in WCC will show positive result of presence of infection in body but commonly, WCC is normal in the early febrile phase. HCT is early determination of plasma leakage. Increase in HCT will show that patients is losing control of their blood flow haemostasis but physicians must first set patient's baseline during early term of infection since administration of fluid replacement therapy may affects the result. In dengue infection, thrombocytopaenia is common parameter. As disease progress, the number of white blood cell may decrease abruptly.

In Liver Function Test, AST keeps significantly inclined as compared to ALT that keep track of failing in function of liver. As disease progress from DF to DHF, elevated liver enzymes is common and expected.

Diagnostic test


In working paper for the Scientific Working Group on Dengue Research done by Buchy and his colleagues (2006), there are three techniques to detect DENV in organism's system. There are technique for virus isolation and identification, serological method and molecular method.

Virus isolation and identification

In technique for virus isolation and identification, it is the only way to diagnose viral infection in early stage. Serotype of DENV is identified after viral amplification stages in mosquito cell lines by using serotypes specific monoclonal antibodies. The limitation of this technique is it only sensitive when relatively high level of infectious particles in serum. A few cell lines can be used in this technique that are mosquito cell line C6/36 (Igarashi, 1978), Aedes Pseudoscutellaris cell line AP61, and less efficient Mammalian cell cultures such as Vero cells, LLCMK2 ( Guzman & Kouri, 1996) and so on.

Identification of DENV can be done by using immunofluorescence technique. Serotype-specific monoclonal anti-dengue antibodies are used. However, due to low viral load in serum, some strains are not easily identified (Buchy et al, 2006)

Serological method

The most common used method is serological method (Guzman et al, 2004). In serological method, five tests can be conducted and each of them offers wide variety of advantages as well as limitations. The mentioned methods are Hemagglutination-inhibition (HI), Complement Fixation (CF), Neutralization Test (NT), Immunoglobulin M (IgM), Capture enzme-linked immunosorbent Assay (MAC-ELISA), and Indirect Immunoglobulin G ELISA (Guzman & Kouri, 1996).

In HI, it is the most commonly used due to sensitivity, cost-saving and reliability. HI antibodies remains for long period and this make it entitled to be used in seroepidemiologic studies. By day of five to six post-dengue infections, HI antibody can be detectable to a certain level. Titers of ≥1,280 are an evidence of a current dengue infection. However, level of HI antibody may decline with increase in time. The disadvantage of this test is it is not serotype-specific, thus it is difficult to determine which serotypes had infect patients (Gubler, 1998).

The more difficult to perform test, CF test, is not widely used worldwide. The principle behind this test is that complement is consumed during antigen-antibody reaction. This test is more serotype-specific in primary infection but not in secondary infection (Gubler, 1998).

In NT test, it is more specific and sensitive test. The serum dilution plaque reduction NT is the common used procedure in laboratory. Neutralizing-antibody titers rise equal to or slightly slowly than HI and ELISA antibody titers but more quickly than CF antibody titers (Gubler, 1998).

Mac Elisa technique uses dengue-specific antigens in order to capture of anti-dengue IgM-specifuc antibodies in serum samples. Antigens are obtained from DENV envelope protein in all dengue serotypes. This test is limited since it cannot be used in cases of multiple flaviviruses presence (Buchy et al, 2006).

IgG Elisa use the same antigen as MAC Elisa and it is been used to detect past infection DENV. Multiple dilutions of the sera tested is used in order to determine an end-point dilution and in the result, as high-point dilution is increase, the more severe the level of infection in the host body is (Buchy et al, 2006). This test is simple and simple to carry out and can be used in high-volume assay but yet incredibly nonspecific as well as show cross-sensitivity among flaviviruses analogous to HI test (Gubler, 1998).

Molecular method

This method is considered new diagnostic technology. Generally, there are two assays that demonstrate the ability to diagnose DENV that are reverse-transcriptase polymerase chain reaction (RT-PCR) and real-time RT-PCR.

Lanciotti et al (1991) had developed rapid detection and typing of dengue viruses from serum samples by RT-PCR technique. There a few steps need to be accomplished before researcher can determine which genotype of DENV is circulating. First and foremost, RNA extraction from DENV-infected cell of the serum sample is obtained before amplified. In amplification step, we need to select and synthesis of oligonucleotide primers, D1 and D2. After first amplification step is complete and DENV is successfully typing by dot blot filter hybridization, second amplification reaction is initiated by conducting similar step as before. A few advantages of this assay are it is rapid, easy to conduct, sensitive and reproducible. However, it should not replace virus isolation method (Gubler, 1998).

In one-step assay, real-time PCR, it uses pair of serotype-specific primers and probes. It can eliminate electrophoresis by substitute it with fluorescent probe. It present in either 'singleplex' or 'multiplex'. All four serotypes can be identified without introducing contaminant during sample manipulation in multiplex assay. Real-time PCR can identify the severity of disease since diagnosticians can know viral load in one's serum sample (Buchy et al, 2006).

Sign and Symptom

Many dengue patients develop fever after infection. According to WHO, in infants and youths, they often have undifferentiated febrile disease accompanied by rash that can be depend on severity of cases and day of post-infection as shown in figure 4, while older children and adults may have a mild febrile condition but other normally have high fever, throbbing headache, pain behind the eye, myalgia and arthralgia as well as rash. Mild bleeding such as nose or gum bleed and easy bruising also may occur during DF (CDC, 2011). Some patients may report itching and abnormalities in the sense of taste, normally metallic taste. Moreover, in certain cases, encephalitic and encephalopathic manifestation also may occur, including lethargy, confusion, seizure, nuchal rigidity and paresis.

Figure 4: Symptom of dengue according to day of post-infection. Adapted from

DF if not managed properly may progress to DHF (Guzman & Kouri, 2002). In more severe cases, DHF, clinical manifestation is same with DF but patient may experience sudden onset of fever and their body temperature may reach until 41 °C. Coughing and sore throat might or might not occur. These symptoms may followed by hemorrhage, especially at skin, in form of rash that can be either maculopapular, patechial or erythematous, hepatomegaly, circulatory collapse, and febrile convulsion when fever is down. Another symptom such as vomiting, severe abdominal pain, black stools and breathing difficulty may occur. There are four compulsory criteria in clinical case classification of DHF. They are fever or past history of sudden onset of fever, thrombocytopenia (100.000/mm3 or less), hemorrhagic sign, and objective evidence of "leaky capillaries", including low albumin, elevated hematocrit more or equal to 20 per cents from baselines, and pleural or other effusions (Avila-Aguero et al., 2004; Phuong et al, 2004; WHO, 2009).

If symptoms are not well-managed or treated, DHF may progress to DSS in day 12 that can lead to death due to circulatory failure. In DSS, clinical manifestation is quite same but more severe. Patients may experience restlessness, cold due to weak blood circulation, pale skin and low pulse pressure (less than 20 mm Hg) as well as weak rapid pulse (WHO,2009).

Management of disease


Most treatment of dengue is symptom-based treatment. There is no definite treatment of dengue until now. According to Malaysia Clinical Practice Guidelines (CPG), in adults, there is a stepwise approach on outpatient management of dengue infection. In first step, overall assessment in term of history, physical examination, and investigation will be done by attended health care professional. In history part, health care professional will ask patient about their onset of illness, assess for any alarm signal, diarrhoea, bleeding, change in mental alertness and important relevant histories. Besides history taking, physical examination also will be done in term of mental state, hydration status, haemodynamic status, abdominal tenderness, occurrence of bleeding and Tourniquet test. Tourniquet test is the test that indicate haemorrhagic tendency. A positive result that is when 20 or more petechiae per 2.5 cm square are observed and it will indicate haemorrhagic tendency. Further investigation will be done by assess FBC and HCT as well as dengue serology test.

In second step, diagnosis, disease staging and severity assessment can be conducted. Bases on step one consideration, the attended clinicians should be able to verify dengue diagnosis, grading the illness, hydration and haemodynamic condition of patients as well as decide whether patient must be admitted to the hospital or not. Before patient is admitted to ward, clinician should consider total assessment of the patient which are patient with symptoms of alarm signal, bleeding presentation, cannot tolerate oral fluids, oliguria, and seizure. Signs of dehydration, shock, and any organ failure as well as in special situations such as patients with co-morbidity, elderly, pregnant mother and social factor are another consideration before patient can be admitted. All of these factors might be accompanied by laboratory criteria such as increase in HCT but thrombocytopenia.

In step three, plan of management must be initiated. District health office must be notified through phone and followed by disease notification form. If admission is necessary, health care providers need to stabilize the patients at the primary care facilities before transfer and communicate with the receiving institution before transfer to notify them about patient attendance. If no admission is required, frequent follow up is necessary from day three of illness onwards until the patients become afebrile for at least 24 to 48 hours without any antipyretics medication.

In dengue patients who not require to be admitted, home care advice should be given according to Malaysia CPG. Adequate bed rest, sufficient fluid intake (more than five glasses for a regular person), take paracetamol (not more than four grams per day), and tepid sponging are among advises can be given to patients. Avoidance of NSAIDS and antibiotic ingestion is compulsory advice need to given to patients.

Patients that present with alarm signal may experience signs such as constant vomiting, abdominal pain or tenderness, fluid buildup in certain body part such as in abdomen and lung, bleeding at mucosal site, malaise, lethargy, hepatomegaly (enlargement of liver size more than 2 cm), and laboratory confirmation of HCT increment and thrombocytopenia.

In patient who required fluid administration, especially in patient with warning signs, patients may improve with early intravenous rehydration. However, some might not and deteriorate to severe stage. Health care professional supposed to obtain a baseline HCT prior to fluid therapy and administer crystalloids solution such as 0.9 per cents saline to patients that presented with warning signs. Crystalloid regimes may begin with five to seven ml/kg/hour for one to two hours, subsequently reduce to three to five ml/kg/hour for two to four hours and then further lessen to two to three ml/kg/hour or less depend on patient response to treatment. If patient continue to get worse, clinicians may consider increasing the infusion rate and this must depend on patient's HCT level.

In non-shock patient, which is DHF grade I and II, patient can be advised to take plenty of oral fluid if patient is haemodynamically stable and not vomiting, but if level of HCT is increasing, IV fluid is recommended. However, in DSS patient that is DHF grade III and IV, clinician must supervise them in ICU, whereby fluid resuscitation must be initiated without delay. Severity of shock will determine volume of fluid resuscitation and can vary from 10-20 mL/kg IBW. Rate of infusion must be monitored carefully and titration of dose must be according to clinical response. Clinical parameter as well as laboratory parameter may indicate whether fluid resuscitation is enough or not. If patients still deteriorate after two cycles of fluid resuscitation with crystalloids, patients may need to be administered with colloids in the third cycle. Gelatin solution and starch solution is colloids of choose in dengue therapy. Consider any bleeding manifestation if all fluid management therapy is failed to show any positive effects.

In patients who haemorrhage is suspected, haemostasis management must be implemented to prevent any blood loss that further will lead to circulatory collapse. Drop in HCT level is an indicator of haemorrhage presentation. Patient may need blood transfusion in severe cases. Transfusion of five to ten ml/kg of fresh-packed red cells or 10 to 20 ml/kg of fresh whole blood at adequate rate might be beneficial in significant bleeding patient. Patients with DHF or DSS need no prophylactic transfusion of platelets and fresh frozen plasma since no effects has been documented on bleeding outcome.


Dengue-infected patient is advised to consume plenty of water, especially those who experience febrile disease in order to reduce body temperature to tolerate range. Patients also advised to bed rest during recovery period. Preventive measure must be taken to prevent further mosquito bite by usage of insecticide sprays, mosquito nets and so on might be helpful. In traditional belief, crab soup can be used to treat dengue. HPA claims that through their Jawi Herbs, one of their products which are herb tea that contain pennywort can be used in dengue treatment. However, it must be concentrated preparation by immerse ten sachets of herbs tea in a jug and must be drink within 24 hours. Another herbs that believe can treat dengue symptom is raw papaya leaves juices. In Philippines, one species of local weed that Filipinos used to call Tawa Tawa or it scientific name is Eurphobia hirta is believed to be useful in management of dengue fever. This is still on-going research on this species of herbs due to it benefits.

2.2 Knowledge, Awareness and Practices (KAP) studies of dengue

In Puerto Rico, study on belief and practices about dengue was conducted by Pérez-Guerra et al (2003) in order to seek discrepancy among man and women of specific group with or without history of dengue infection in term of knowledge, beliefs, attitude and practices about dengue prevention and to compare the obtained results with the previous, 2001 study. From the obtained results, women were more concerned as regards of dengue threat, more educated about disease and it anticipation, and suggested utilize of repellents more often compared to those same group without history of dengue. In Puerto Rico's culture and norms, responsibility for the household and wellbeing of family member is in women's hand while men are taking part in domestic and health affair. In order to target this population, different approaches need to be implemented in both genders. Experience is the best way to educate people. This is proven by those who had been diagnosed with dengue before, he or she are more knowledgeable about dengue and it prevention as well as more concern about other people risk of infected by this virus.

In one of tropical country, Jamaica, where is dengue had became major health dilemma, KAP study was performed in 2010 by Faisal Shuaib et al. Most of participants are unable to determine accurate signs and symptoms of DF similar as previous designated study done in Thailand by Leera et al. 54.4 percents, 46.6 percents and 28.5 percents of respondent responds to had at least 80 percents on knowledge, attitude and prevention on dengue, respectively. From the figures, even though more than half of respondents had knowledge about dengue, but only small percentages of them willing to put in action to practice preventive action against dengue. Regarding educational backgrounds profile, as level of education higher, score of knowledge also rose. As a conclusion, a good knowledge does not guarantee a positive attitude and practice against dengue.

374 peoples willing to participate in KAP study in Male', Maldives with 60 percents of them are female. Nahida (2008) in her survey found that most of them are educated in level of primary (43.9 percents) and secondary (43.9 percents) education. Only 12.2 percents are graduate or post-graduate and most of them are employed. 80.5 percents had history with dengue either directly or indirectly. Most of them had heard about dengue. Respondent's knowledge of dengue is low even though many of them, about 42 percents claimed to receive their information from television and radio. This proven by 46 percents of them scored in range of low knowledge. However, in term of attitude, 42.5 percents of them has positive attitude. Only 8.8 percents of them have good practice and most of them (48.1 percents) fall in fair practice. From the analyzed data, no corresponding relationship between practice level towards dengue and history of dengue either directly or indirectly. Compared to males, female sex has more level of practice towards dengue.

Ahmed Itrat and his co-researchers (2006) were successfully distribute questionnaire to the 447 respondents that were willing to take part in their cross-sectional study title knowledge, awareness and practices regarding dengue fever among the adult population of dengue hit cosmopolitan in Civil Hospital (CHK) and Aga Khan University Hospital (AKUH) located at Karachi, Pakistan. 89.9 percents had heard of dengue and majority (81.5 percents) agreed of fever is the common symptoms. Data shows that most of respondents are aware of this fatal disease however, something must be done in order to educate those who never heard of dengue. In aspects of degree of knowledge, more than half of them knew that vector breeds in standing clean water, most of them agreed that mosquito spray (54.9 percents) and mosquito mat, coil or liquid vaporizer (50.1 percents) are the preventive measure that can be taken to prevent against mosquito bite. Some of the respondents, due to the high prevalence of malaria, assume Anopheles mosquito is identical as Aedes mosquito in term of characteristics and habitat. As previous studies, television is the major sources of information about dengue.

In other study by Madiha Syed and colleagues in Karachi, Pakistan on knowledge, attitudes and practices regarding DF among adults of high and low socioeconomic groups, 400 respondents, which are fairly distributed among two socioeconomic statuses and 244 of them are males, were involved. 35.5 percents of chosen respondents had sufficient knowledge about dengue. Those that have sufficient knowledge are 68 percents from high socioeconomic status and 32 percents from low socioeconomic status. Many respondents agreed that government should take accountability to prevent spread of disease and preventive measurement. Meaningful correlation had been detected between knowledge and education backgrounds (p=0.004) and socioeconomic status (p=0.02). People with high socioeconomic background had more knowledge, high attitude and practice more than people with low socioeconomic backgrounds.

In another part of Pakistan, in the Multan district, Naeem-Ullah and Akram (2007) disclosed that 23.7 percents from 270 peoples are illiterate, graduate and above. This data is important because there are a significant relationship between level of education and awareness as well as between level of education and knowledge. Percentages show that significant number of respondents from Multan population are not well-educate about dengue. This proven by only 21.5 percents of them knew that dengue is transmitted by mosquito and 12.6 percents agreed that vector is breed in rainy season. 68.15 percents were aware of DF and out of them, 82.6 percents said that the primary resources of their information are radio and television followed by printed media and friends. Similar as other part of world, preventive measure such as fans, mats and coils are taken to prevent mosquito bite.

In 2009 published paper on knowledge, attitude and practice regarding dengue among people in Pakse, Laos, 230 subjects that had experienced from DF and/or were treated within less than two years from nine villages are involved in this study. From the distributed questionnaire, analysis shows that only a few of them (4.3% percents) are illiterate and most of them are housewife (32.6 percents) and merchant (30.4 percents). In term of knowledge regarding dengue, a few parameters are measured. In term of symptoms, 75.2 percents of respondents agreed that fever is symptom of dengue followed by 18.7 percents agreed on skin rash. 93.5 percents knew that mosquito bites is mode of transmission of dengue and 65.2 percents agreed that mosquitoes are bite in daytime. Most of the respondents were aware that DF is severe disease and they need to seek medical attention if they affected. As a conclusion of study done, a good knowledge and attitude of dengue does not ensure good practice to prevent dengue (Soodsada et al, 2009).

In Ang Thong, Thailand, cross-sectional KAP study on DHF had been conducted by Leera et al (1999). Throughout this a year of period study, 131 caretakers took part in this survey since this study involves dengue virus-infected, non-dengue virus-infected and healthy children under age of fifteen years old. From the observed results, ratio of attack rate of 1.5:1 between boy and girl shows that male is susceptible to dengue virus attack compared to female. In term of knowledge, caretakers that has history of dengue had more knowledge about dengue (the transmission vector, breeding site and so on) compared to those who had no history of dengue. Even though most of them have false attitude towards signs and symptoms of dengue (p=0.006), but they have positive attitude in transmission, treatment and prevention of dengue. In last part of survey, results show that the caretakers of dengue patient scores better than other two groups in aspect of practice of prevention, treatment and control of dengue. Caretakers with history of dengue had more knowledge, positive attitude and apply good practice compared to non history and healthy population.

Indonesia is one of south-east Asia countries that also encounters dengue epidemic problem. In August 2000, one of the researchers from US Naval Medical Research Unit No.2, Beckett and his co-researchers conduct a study on enhancing knowledge and awareness of dengue during a prospective study of dengue fever. Employees from two plants that consist of 1373 males and 967 females were involved in this pre- and post-test that includes comparison between before they were given information about dengue and after 18 months after information were given to them. System of point was given that further categorized as excellent until very bad. On the pre-test, most of respondent scored fair (39.9 percents) and good (38.4 percents), and on the post-test, average score became better with 42.5 percents scored good and 23.8 percents scored very good. This improvement is highly correlate with level of education (Pearson rank correlation =0.389, p=0.01).

In another study done in 2004 by Acharya et al, majority of residents of an urban resettlement colony of south Delhi are aware of dengue. Survey was done and divided into four sections: demographic profile, knowledge about dengue, practices on control of dengue, and sources of information regarding dengue. In socio-demographic status, 20.2 percents of the population was in range of 35 to 44 years old with 64.1 percents of female take parts in this study. 25.6 percents from them are illiterate and only 5.9 percents are graduate and above. In term of knowledge about dengue, 90 percents out of the 641 respondents of the selected population had heard about dengue with 68 percents of them mention the most common causes of dengue is mosquito bite, 48 percents dirty drinking water, and 20 percents environment. 68 percents knew that dengue can be spread but only 55 percents knew that mosquito bite is mode of spread. 23.4 percents of the populations have no knowledge on symptom of the dengue, more than 90 percents knew fever alone or 19 percents say it accompanied by chill and 38 percents say headache are one of the symptoms of dengue. In last part of the survey, which are sources of information regarding dengue, from 577 multiple responses, 102.58 percents were educated from mass media (television, newspaper, magazines, radio) while other sources are through health personnel, banners, school, friends and neighbours and others sources.

In Malaysia, Wan Rozita and her colleagues had done cross-sectional study on knowledge, attitude and practice in urban Malay housing area that was done in Kampung Datuk Keramat, Kuala Lumpur. From this three months survey that was done from August to November 2005, revealed that there is weak positive relationship between knowledge and practice (r = 0.271, p = 0.002) but insignificant correlation between attitude and practice as well as between attitude and knowledge (p>0.05). From 133 respondents, 79.7 percents of them never contract or had any past history of dengue. 98.5 percents had heard of dengue with 85 percents said that television is the main sources of information. In this study area, slightly better percentage of participants had heard about dengue if compared to in South Delhi reported by Archarya, A. 94.7 percents said that precautionary measures were required to prevent dengue fever and 96.2 percents were willing to work hand-on-hand on extermination program of Aedes mosquito vector. Respondents that have history of dengue either themselves of having family members with dengue shows that high reliability in knowledge, attitude and practice compared to those who never had history of dengue. From this study, it can be concluded that good knowledge and good practice are not contribute to correlation of good attitude.

2.3 Impact of Dengue

In Singapore, a study on post-infectious fatigue syndrome in dengue infection was done by Seet et al (2006) in order to access one of the symptoms at acute stage of dengue. In this study, frequently appeared clinical manifestations are fever, poor appetite, tiredness, headaches, nausea, chills, muscle, pain, and rashes. This supported by laboratory features (hematologic parameters: white blood cell count, hemoglobin, hematocrit, and platelet) and biochemistry parameters (level of sodium, potassium, urea, creatinine, albumin, total bilirubin, aspartate transaminase, alkaline transaminase, and lactate dehydrogenase). However, there are no significant relationship between hematologic and biochemical parameters with severity of dengue. From the obtained results, 19.7 percents from 127 patients have DHF and remaining 80.3 percents were suffered of DF. 24.4 percents feel fatigue and risk factors for development of fatigue are increased age, female, and the presence of chills as well as absence of rashes. Additional factors that can predispose fatigue syndrome in female sex are function of reproductive, genetic make-up, and the way they deal with their stress.

Study on the economic impact of dengue hemorrhagic fever on family level in Southern Vietnam in 2005 was conducted and revealed that family with child having DHF require spending large amount of money during course of therapy. In average, the cost is about USD 32.73 for direct cost and for indirect cost is USD 28.73. Direct cost takes account of hospital bills, physician appointment admittance fees, and laboratory tests, while indirect cost covers loss of earnings, transport and food because most of children that seeks for treatment are accompanied by their parents or caretaker. Compared to gross national income per capita of Vietnam (USD 620), the average cost of USD 61 to teat dengue infected child is considered as large figure. Between severities of the disease, they require different cost of treatment that must be paid by child's family (Harving, 2007).

In tourism industry, numerous popular tourist destinations such as Indonesia, Thailand, Malaysia and other magnificent tropical countries encountered dengue epidemics problem especially during raining season. Travelers who visit those outbreak areas are at high risk to develop DF and it ought to be suspected in those patients who visit physician when they returned to their homeland. In Korea, data collected by Korea Centers for Disease Control and Prevention (KCDC) throughout year of 2001 to 2008 reported that 22 cases of pediatrics DF and all of them were imported cases. 65.6 percents from 517 patients that visited pediatric infectious disease clinic at Samsung Medical Center were took part in this questionnaire and out of them, 29.8 percents has international travelling history within two years. From those data, there are seven patients present one of dengue symptoms and only four of them were suspected of DF due to presented symptoms and history of travelling to epidemic areas. Number of imported dengue rise as number of travelers visiting epidemic areas increasing (Soo et al, 2010).

2.4 Summary

Since dengue can cause many complications and impacts, as part of community, Malaysian should take preventive measurement to prevent transmission and epidemicity of DENV. Furthermore, when you experience some of the symptoms of dengue, ignorance is the attitude that needs to be eliminated before disease progress to more complicated cases. Seek advice from you physicians before self-medicated with over-the-counter drug(s).