Introduction
Dengue fever is a mosquito-borne viral illness caused by dengue virus (DENV) and predominantly affects populations in tropical and subtropical regions. Infection is frequently asymptomatic or produces a self-limited febrile illness; when symptomatic, clinical onset typically occurs 3–14 days after exposure and commonly includes high fever, severe headache, arthralgia, nausea or vomiting, pruritus, and a characteristic maculopapular rash. Laboratory abnormalities such as leukopenia and thrombocytopenia are common. A small proportion of infections progress to severe dengue—historically referred to as dengue hemorrhagic fever or dengue shock syndrome—characterized by plasma leakage, haemorrhage, marked thrombocytopenia, and potentially life-threatening hypotension.
DENV comprises four antigenically distinct serotypes (DENV-1 to DENV-4) within the Flavivirus genus, a group of enveloped, positive-sense single-stranded RNA viruses that also includes Zika, West Nile, and yellow fever viruses. The principal vector is the peridomestic mosquito Aedes aegypti, which thrives in urban environments and breeds in man-made water containers. (1)
The widespread distribution of Aedes mosquitoes has enabled dengue to become one of the most significant mosquito-borne viral diseases globally. It is estimated that nearly 50% of the world's population resides in regions where dengue transmission occurs, with approximately 100–400 million infections reported each year. Laboratory confirmation of dengue depends on the stage of illness. During the early phase of infection, viral detection methods such as reverse transcription-polymerase chain reaction (RT-PCR) are commonly used to identify viral RNA, whereas serological tests are employed later to detect dengue virus-specific antibodies. Preventive strategies primarily emphasize reducing mosquito populations through vector-control programs and limiting human exposure by adopting personal protective measures against mosquito bites.
At present, two dengue vaccines have received regulatory authorization. Dengvaxia, introduced in 2016, is recommended mainly for individuals with evidence of previous dengue virus infection because vaccination of seronegative individuals has been associated with an increased risk of severe disease following subsequent infection. Qdenga, approved in 2022, is indicated for children aged four years and older, adolescents, and adults in accordance with regional regulatory recommendations.
No antiviral medication has yet been approved for the treatment of dengue infection. Clinical management therefore remains supportive and is guided by disease severity, ranging from symptomatic relief in uncomplicated cases to careful fluid replacement, continuous clinical assessment, and hospitalization for patients who develop severe dengue or warning signs. Although decades of research have advanced dengue vaccine development, producing a vaccine that is both broadly effective and consistently safe across different populations remains difficult because of the complex immune responses induced by the virus, particularly the potential for antibody-dependent enhancement. Consequently, dengue continues to represent an increasing public health challenge in many endemic and emerging regions worldwide. (2)
Fig-1: History of dengue fever
Severe dengue
According to the World Health Organization (WHO) International Classification of Diseases, severe dengue is defined by the presence of one or more major clinical manifestations, including extensive plasma leakage, severe bleeding, or impairment of vital organ function. This severe form of the disease can develop suddenly and most commonly emerges during the critical phase, often after the patient's fever has resolved. Extensive plasma extravasation from the capillary bed can precipitate profound hypotension and hypovolemic shock; affected patients may develop pleural effusions or ascites, hypoproteinemia, and hem concentration. Severe dengue constitutes a medical emergency because it can cause multi-organ impairment and death if not promptly recognised and managed. (3)
Clinical differentiation between mild dengue and other common febrile illnesses can be challenging. Early dengue may mimic influenza, measles, chikungunya, or Zika virus infection. Because dengue, chikungunya, and Zika share Aedes mosquitoes as vectors and are often co-endemic, concurrent infection with more than one arbovirus is possible.
History
The earliest probable description of dengue appears in a Chinese medical text from the Jin dynasty (266–420), which described a “water poison” associated with flying insects. The principal vector, Aedes aegypti, expanded beyond Africa between the 15th and 19th centuries, a spread facilitated by the slave trade and the growth of international commerce. Accounts of dengue-like epidemics date from the 17th century, and outbreaks in Jakarta, Cairo, and Philadelphia in the 18th century were likely dengue. Throughout the 19th and early 20th centuries dengue was probably endemic in many tropical urban centres, although major epidemics were relatively uncommon.
Fig-2: Time line of dengue
The substantial rise in dengue incidence during and after the Second World War has been attributed to wartime disruption and subsequent urbanization in Southeast Asia. Introduction of new serotypes into areas with existing endemic transmission precipitated outbreaks of more severe disease. The hemorrhagic form of dengue was first documented in the Philippines in 1953 and, by the 1970s, had emerged as an important cause of childhood mortality in Southeast Asia.
In Central and South America, Aedes populations had been largely eradicated during the 1950s eradication campaigns; however, these programs were discontinued in the 1970s and by the 1980s dengue re-established transmission across the region, becoming hyperendemic and causing recurrent epidemics. Dengue incidence has continued to rise in the 21st century as Aedes vectors expand their geographic range, driven in part by ongoing urbanization and in part by climate warming. (4)