Research Article: Rapid Diagnostic Tests for Dengue Virus Infection in Febrile Cambodian Children: Diagnostic Accuracy and Incorporation into Diagnostic Algorithms

Date Published: February 24, 2015

Publisher: Public Library of Science

Author(s): Michael J. Carter, Kate R. Emary, Catherine E. Moore, Christopher M. Parry, Soeng Sona, Hor Putchhat, Sin Reaksmey, Ngoun Chanpheaktra, Nicole Stoesser, Andrew D. M. Dobson, Nicholas P. J. Day, Varun Kumar, Stuart D. Blacksell, Ernesto T. A. Marques.

Abstract: BackgroundDengue virus (DENV) infection is prevalent across tropical regions and may cause severe disease. Early diagnosis may improve supportive care. We prospectively assessed the Standard Diagnostics (Korea) BIOLINE Dengue Duo DENV rapid diagnostic test (RDT) to NS1 antigen and anti-DENV IgM (NS1 and IgM) in children in Cambodia, with the aim of improving the diagnosis of DENV infection.Methodology and principal findingsWe enrolled children admitted to hospital with non-localised febrile illnesses during the 5-month DENV transmission season. Clinical and laboratory variables, and DENV RDT results were recorded at admission. Children had blood culture and serological and molecular tests for common local pathogens, including reference laboratory DENV NS1 antigen and IgM assays. 337 children were admitted with non-localised febrile illness over 5 months. 71 (21%) had DENV infection (reference assay positive). Sensitivity was 58%, and specificity 85% for RDT NS1 and IgM combined. Conditional inference framework analysis showed the additional value of platelet and white cell counts for diagnosis of DENV infection. Variables associated with diagnosis of DENV infection were not associated with critical care admission (70 children, 21%) or mortality (19 children, 6%). Known causes of mortality were melioidosis (4), other sepsis (5), and malignancy (1). 22 (27%) children with a positive DENV RDT had a treatable other infection.ConclusionsThe DENV RDT had low sensitivity for the diagnosis of DENV infection. The high co-prevalence of infections in our cohort indicates the need for a broad microbiological assessment of non-localised febrile illness in these children.

Partial Text: The number of people at risk of infection with one or more of the four dengue viruses (DENV) has increased exponentially over the past half-century, with the immuno-pathological complexity of DENV hampering vaccine design [1–4]. DENV infection first manifests as a non-specific febrile illness before either resolving, or progressing to severe disease characterized by endothelial activation, increased vascular permeability and impaired haemostasis [2,5]. Early diagnosis and identification of those at risk of severe disease is therefore important, leading to the development of rapid diagnostic tests (RDTs) to DENV antigens and anti-DENV antibodies [6–12], and previous work incorporating clinical and laboratory features of the disease (but not RDTs) into decision algorithms [13–18].

During a single wet season in Cambodia a DENV RDT had a positive predictive value of 53% and negative predictive value of 88% for reference assay positive DENV infection in febrile children admitted to hospital. The high negative predictive value indicates that a negative DENV RDT may practicably “rule-out” DENV infection in this cohort (but not “rule-out” other co-infections).



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