Clinical and Laboratory Diagnosis of Dengue Virus Infection

Abstract

Infection with any of the 4 dengue virus serotypes results in a diverse range of symptoms, from mild undifferentiated fever to life-threatening hemorrhagic fever and shock. Given that dengue virus infection elicits such a broad range of clinical symptoms, early and accurate laboratory diagnosis is essential for appropriate patient management. Virus detection and serological conversion have been the main targets of diagnostic assessment for many years, however cross-reactivity of antibody responses among the flaviviruses has been a confounding issue in providing a differential diagnosis. Furthermore, there is no single, definitive diagnostic biomarker that is present across the entire period of patient presentation, particularly in those experiencing a secondary dengue infection. Nevertheless, the development and commercialization of point-of-care combination tests capable of detecting markers of infection present during different stages of infection (viral nonstructural protein 1 and immunoglobulin M) has greatly simplified laboratory-based dengue diagnosis. Despite these advances, significant challenges remain in the clinical management of dengue-infected patients, especially in the absence of reliable biomarkers that provide an effective prognostic indicator of severe disease progression. This review briefly summarizes some of the complexities and issues surrounding clinical dengue diagnosis and the laboratory diagnostic options currently available.

Burden of dengue among febrile patients at the time of chikungunya introduction in Piedecuesta, Colombia

“…This same pattern of age distribution has been observed in an acute febrile illness survey (AFI) conducted in Puerto Rico , and in a cross‐sectional study in Brazil . Possible explanations include the consideration that older people were susceptible to the recently introduced chikungunya and that older participants were already sensitised by the endemic presence of dengue . Chikungunya has been previously documented in older people and speaking for this pattern are (i) an unclear physiological mechanism and (ii) the likelihood of comorbidities at older ages , which in turn could be translated into a more‐than‐average‐ symptomatic condition that resulted into a differential heath seeking behaviour pattern.…”

Dynamics of nonstructural glycoprotein‐1 in dengue patients presenting with different clinical manifestations from 1986 to 2012 in Rio de Janeiro, Brazil

“…Patient data and T A B L E 1 Summary of demographic, clinical, and virological characteristics of the study population (n = 202) (1986-2012, Rio de Janeiro, Brazil) The detection of NS1 represents a better approach for the diagnosis of the acute phase of dengue when compared with the levels of viremia. 8,9,[18][19][20][21]23,24,26 In addition to NS1 being detectable throughout the febrile phase, it is more stable in solution than the viral genome, facilitating the handling and storage of the sample. NS1 is actively secreted by infected eukaryotic cells and must be present very early and in high levels during the viremic phase of infection, characterized by an early peak of viremia that decreases after the 4th day of fever onset.…”

Public health aspects of Dengue virus infection relevant to Australia

“…Flavivirus serology is complicated by cross reactivity within the genus and infection with a second flavivirus (ZIKV, JEV, Yellow fever virus) can cause a misleading rise in antibody titre of the previously encountered flavivirus (immune recall or original antigenic sin). This is caused by cross-reactive epitopes on the flavivirus E protein 11 . IgG is of little value in the diagnosis of recent infection unless paired sera are tested.…”

“…This is especially problematic in Brazil since 2015, where ZIKV infections occur on a background of endemic DENV. It is recommended to do serology plus NS1 antigen to improve diagnostic accuracy, and reduce misdiagnosis of ZIKV and DENV 11 .…”