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Dengue virus (DENV) infection is currently the most serious mosquito-borne viral disease. DENV is a single-stranded positive-sense RNA virus whose genome encodes three structural and seven nonstructural (NS) proteins. Depending on the different antigens carried, DENV is classified into four serotypes, which induce antibodies against each other without cross-neutralization reactions. Female Aedes aegypti mosquitoes are responsible for transmitting the dengue virus, and they are found mainly in tropical and subtropical areas. However, an increasing number of dengue outbreaks have shown DENV to be transmitted by the temperate Aedes albopictus mosquito, which opens the possibility of further geographic invasion of dengue. It is estimated that as many as 390 million dengue virus infections occur each year, with more than half a million hospitalizations and 25,000 deaths.
The clinical presentation of patients infected with DENV ranges from mild fever to classic dengue fever with hemorrhage (DHF) or dengue shock syndrome (DSS). Typical dengue disease is an acute infection with clinical manifestations appearing 4-10 days after the bite of a virus-carrying mosquito, characterized by elevated temperature, severe headache, retro-orbital pain, malaise, severe joint and muscle pains, nausea and vomiting, and a rash that develops 3-4 days after the onset of fever. Patients are immune to subsequent dengue virus invasion corresponding to specific serotypes after initial infection. Severe dengue disease is mainly seen in individuals experiencing different serotypes of infection, with patients experiencing the same symptoms as primary dengue in the early stages of the disease, followed by a rapid deterioration of the disease during the febrile period, with the development of hemorrhage, thrombocytopenia, ascites, pleural effusions, elevated hematocrit concentrations, a precipitous drop in body temperature with profuse sweating, and hypoadrenocorticism. Current clinical treatment is based on symptomatic support.
Figure 1. Classification of dengue disease progression
(Source: Muller DA, et al. 2017)
Biomarkers used for diagnosis include the virus itself, the viral product, or the host's immune response to viral infection. Virus isolation, the traditional diagnostic method for detecting DENV infection, has been gradually replaced by reverse transcription polymerase chain reaction (RT-PCR), a PCR-based method that can diagnose DENV on the same day or the next day during the acute phase of the disease. RT-PCR has good specificity and sensitivity, and the assay is rapid, but is not applicable in remote areas where resources are scarce. The viral protein S1, secreted from infected cells, is an ideal target for clinical use, circulates in high concentrations in the blood of infected individuals, and can be detected in primary infections from the onset of symptoms to 9 days or more after onset. NS1 can be detected before an antibody response occurs, and levels of NS1 correlate with viral titers and are therefore considered an alternative marker for viremia. NS1 testing in patients with secondary infections is limited because NS1 cross-reactive antibodies rise rapidly during the acute phase of secondary infections. Due to the different kinetics of each biomarker, testing by one method alone does not guarantee accurate detection of dengue infection, and combining the biomarkers provides better detection of DENV in patients at different stages of infection.
Figure 2. Timeline of dengue biomarker appearance in patients experiencing primary and secondary infection
(Source: Muller DA, et al. 2017)
References
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Dengue in Timor-Leste during the COVID-19 phenomenon
Front Public Health
Authors: da Cruz ZV, Araujo AL, Ribas A, Nithikathkul C.
Long-term efficacy and safety of a tetravalent dengue vaccine (TAK-003): 4·5-year results from a phase 3, randomised, double-blind, placebo-controlled trial
Lancet Glob Health
Authors: Tricou V, Yu D, Reynales H, Biswal S, Saez-Llorens X, Sirivichayakul C, Lopez P, Borja-Tabora C, Bravo L, Kosalaraksa P, Vargas LM, Alera MT, Rivera L, Watanaveeradej V, Dietze R, Fernando L, Wickramasinghe VP, Moreira ED Jr, Fernando AD, Gunasekera D, Luz K, Oliveira AL, Tuboi S, Escudero I, Hutagalung Y, Lloyd E, Rauscher M, Zent O, Folschweiller N, LeFevre I, Espinoza F, Wallace D.
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