*2.1.1. Biosensor platform*

Clinical symptoms typically appear 4–7 days following the mosquito bite and may persist for 3–10 days. Clinical manifestation of dengue varies from asymptomatic to acute febrile illness with headache, vomiting, severe myalgia, rash, retro-orbital pain, and arthralgia [4–6]. Classically, dengue was categorized as dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Nevertheless, classification was revised by the WHO in 2009 and classified it as dengue with or without warning signs. This version of classification divides dengue into three clinical phases: febrile, critical, and recovery phases [7, 8]. In the febrile phase, patient develops high fever due to acute viremia, and this phase lasts for 2–7 days. Critical phase usually lasts for 2 days and is indicated by plasma leakage, hemorrhage, and low platelet number. If patients survive in critical phase, then they will recover from the disease at the

The spherical and enveloped dengue virus (DENV) which belongs to the family *Flaviviridae* is the causative agent of dengue. This virus is 50 nm in diameter and contains about 11 kb positive-sense single-stranded RNA genome that codes for three structural proteins (capsid, membrane, and envelope) and seven nonstructural proteins [11, 12]. The DENV is transmitted to human by the bite of *Aedes aegypti* and *Aedes albopictus* mosquito which usually breed in the clean water in urban areas [13, 14]. Each serotype of DENV can cause dengue and trigger inimitable immune response in host which provides long-term immunity to that particular serotype but limited and partial immunity against three other serotypes [15, 16]. Although, the four DENV serotypes are antigenically different but genetically are identical as they share

At this time, a tetravalent dengue vaccine has been developed but due to its lack of protection on non-exposed individuals, it is not an effective option. On the other hand, antiviral drugs for curing the dengue are not available; thus, accurate and timely diagnosis is of utmost importance for appropriate management of a patient suffering from severe dengue [19]. However, diagnosis of dengue based on clinical manifestation is quite complicated as the signs of dengue are very common in other febrile illness; therefore, diagnosis is very challenging using this approach [10, 20]. Thus, laboratory confirmation is needed for definite diagnosis. Laboratory confirmation of dengue can be obtained using several techniques such as virus isolation, polymerase chain reaction (PCR)-based detection of viral genome, nonstructural protein 1 (NS1) antigen detection, and serological detection of dengue-specific antibodies such as IgM and IgG [21]. Nevertheless, effective application of each diagnostic

The WHO set "affordable, sensitive, specific, user-friendly, rapid, easy to handle and deliver to those who need them (ASSURED)" as the characteristics of an ideal point-of-care test for resource-limited countries [22, 23]. With the advancement of science and technology, several

third phase known as recovery/convalescent phase [9, 10].

about 65% of their RNA sequences [17, 18].

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

technique depends on the disease stages.

**2.1. Recent advancement in the diagnosis of dengue**

**2. Diagnosis of dengue**

The criteria of point-of-care test resulted attractive for industry and researchers in order to develop and satisfy the qualification of ideal diagnostic test. Therefore, numerous researchers around the world have been working on biosensors in a search of potential point-of-care test as they offer several advantages such as high sensitivity and specificity, simple instrumentation, rapid assay outcome, portability and disposability of developed tools. Several researchers have reported biosensor for the diagnosis of dengue. In this section, we take a glance over current biosensor methods aimed to improve the diagnostic of dengue using different biomarkers.
