**5. The virus**

**Figure 3.** *Aedes aegypti* with its taxonomic characteristics. (a) *Aedes aegypti*; (b) Lyrix at thorax; (c) Clypeus; (d) Proboscis;

**Figure 2.** Difference between *Aedes aegypti* and *Aedes albopictus* (Source: http://www.mdsaude.com/wp-content/uploads/

(e) silvery scales on wing; (f) white stripes on leg.

2012/04/aedes-aegypti-e-aedes-albopictus.jpg).

6 Dengue Fever - a Resilient Threat in the Face of Innovation

Dengue infection is transmitted by dengue virus (DV) which is a member of genus *Flavivirus*. This Arbovirus group of viruses is specifically transmitted via insect vectors. Mature viral particles have diameter of 40–50 nm, spherical shape and 11 kb, having positive single stranded RNA which has a 5′-methyl cap with a single open reading frame. Genus *Flavivirus* has 4 antigenically associated but four distinct serotypes known as DENV-1, DENV-2, DENV-3 and DENV-4 [27, 28]. The serotypes are evolved from a common ancestor and all are considered

[35]. However the exact mechanism of vascular permeability and hemorrhagic fever is not clear. Studies are being oriented to understand these mechanisms specially focusing on the role played by T-cell immune response. High levels of interferon alpha were reported during secondary infection after 1–2 days of fever onset [36] while high concentration of soluble interleukin 2 receptor, interferon γ, soluble CD8 and soluble CD4 interleukin 2 were also

Dengue Fever: A General Perspective http://dx.doi.org/10.5772/intechopen.81277 9

The most commonly occurring DENV infection transits through an asymptomatic or mildly symptomatic course [38]. Symptomatic dengue fever is usually accompanied by headache, malaise, retroorbital pain, arthralgia, and myalgia with a severity that honors "break-bone" fever alternative name of this disease. It lasts from three to 7 days. A small fraction of these patients evolve to the life-threatening clinical form of severe dengue, usually preceded by the appearance of warning signs (see below). All the four viral serotypes cause resembling disease symptoms. In comparison to the previous 1997 version, the WHO revised classification of 2009. This makes more precision towards sensitivity and specificity of dengue cases. While being reported having changed dengue features with the passage of time during treatment; the dengue affected patients are categorized in Group A or Group B. More concern is recommended if symptoms becoming serious for next step of necessary hospitalization [39, 40]. As WHO 1997 version already includes plasma leakage and bleeding; but, however, the WHO 2009 classification entails target monitoring and organ impairment exhibiting the situation more clearly towards future dengue disease cure. Group C category of dengue patients has been explained in a better way in revised classification of WHO version 2009. This version, indeed is a practical guidance and very much helpful in dengue endemic areas especially where medical facilities are lacking. It is worth mentioning that WHO 2009 classification also highlights the other co-existing factors such as pregnancy,

described by researchers during the outset of vascular permeability [36, 37].

child and old age, diseases like diabetes and various social circumstances [41].

**1.** Without warning signs of dengue,

**i.** Group A includes patients without warnings signs,

**3.** Severe symptoms of dengue.

patients:

The WHO 2009 revised dengue classification stratifies disease into the following:

**2.** With warning signs of dengue (i.e., abdominal pain, vomiting, fluid accumulation, mucosal bleed, lethargic condition, liver enlargement >2 cm, and rapid decrease in platelet count), and

Furthermore, three categories have been described in 2 WHO scheme of dengue-affected

**ii.** Group B includes patients with more than one warning sign, and annotated with certain coexisting conditions such as pregnancy, infancy, old age, obesity, diabetes, renal failure,

and chronic hemolytic diseases), and with certain social circumstances,

**6. Clinical aspects**

**Figure 4.** Lifecycle of *Aedes aegypti* (http:/www.ipnc.nc/FCKeditorFiles/Image/entomo\_20.jpg).

causative agent of broadly analogous disease spectrum in humans [29–31]. It consists of ten proteins, out of which three proteins, capsid (C), membrane (M), and envelope (E), play structural role and seven (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5) are identified as non-structural that direct DENV replication. Approximately 17% of these virions are lipid by weight which forms a lipid bilayer between E/M outer shell and the nucleocapsid core [32, 33].

Binding of dengue virus like most of the other viruses to its receptor is regulated by envelop protein (E). In mammalian cells, all the serotypes binds with nLc4Cer, DC-SIGN/L-SIGN, Heparan sulfate as well as Mannose receptors. Additionally DENV-2 serotype also show binding trend with HSP70/HSP90, CD14-associated protein, GRP78 and two other unknown protein receptors. On the other hand DENV 1–3 serotypes can also attach with Laminin receptor while DENV 2–4 serotypes are also found to bind with protein receptor which is unknown [34]. After binding with particular receptors through receptor-mediated endocytosis, virion fuses with acidic lysosomes. Then, the viral particle releases its RNA in the cytoplasm of host cell for the synthesis of viral proteins. After the synthesis of all the required proteins, viral RNA starts generating a minus strand, and then transcription of new plus stranded molecule occurs. Hundreds of copies of viral particles are generated from a single virus particle leading towards cellular damage and even death. RNA-dependent RNA polymerases (RdRps) encoded by the virus itself and other cellular factors catalyze the infection cycle of this virus [35]. However the exact mechanism of vascular permeability and hemorrhagic fever is not clear. Studies are being oriented to understand these mechanisms specially focusing on the role played by T-cell immune response. High levels of interferon alpha were reported during secondary infection after 1–2 days of fever onset [36] while high concentration of soluble interleukin 2 receptor, interferon γ, soluble CD8 and soluble CD4 interleukin 2 were also described by researchers during the outset of vascular permeability [36, 37].
