Prospective Study To Determine Accuracy of Rapid Serological Assays for Diagnosis of Acute Dengue Virus Infection in Laos

Abstract

), we recently evaluated eihgt commercially available immunochromatographic rapid diagnostic tests (RDTs) designed to detect dengue virus-specific immunoglobulin M (IgM) and/or IgG. We found that 6/8 RDTs had sensitivities of less than 50% (range, 6 to 65%), but specificities were generally high. Here, in conjuction with dengue virus serotyping by reverse transcriptase PCR and in the limited-resource setting of Laos, where dengue virus is endemic, we evaluated the same eight RDTs against a previously validated dengue IgM/IgG enzyme-linked immunosorbent assay for diagnosis of acute dengue virus infection. Paired serum samples were collected from 87 patients, of whom 38 had confirmed dengue virus infections (4 had primary infections, 33 had secondary infections, and 1 had an infection of indeterminate status). RDT sensitivity was low, with 7/8 RDTs having admission sample sensitivities of less than 20% (range, 4 to 26%). The majority (6/8) of the RDTs, demonstrated high specificity (>95%). Kappa statistic values ranged from 6 to 54% for the RDTs, demonstrating poor to moderate variation between three operators. No RDT adequately differentiated between primary and secondary dengue virus infections. The findings of this study suggest that currently available RDTs based on the detection of IgM antibodies for the diagnosis of acute dengue virus infections are unlikely to be useful for patient management.Dengue virus infection causes a wide spectrum of diseases, including dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). Patients with dengue virus infection present with signs and symptoms similar to those of other acute tropical febrile illnesses, necessitating confirmatory laboratory diagnosis which is usually based on serology (13). Dengue hemorrhagic fever and DSS, which are more severe clinically, are thought to occur more commonly in those with a secondary infection (7), and early laboratory diagnosis could have prognostic value if accomplished prior to defervescence, the risk period for plasma leakage and shock. During the acute phase of infection, detection of dengue virusspecific immunoglobulin M (IgM) antibodies alone suggests primary infection, and the presence of both IgM and IgG antibodies suggests secondary or later infection. The development of rapid diagnostic tests (RDTs) using immunochromatographic or immunoblotting technologies has provided a mechanism for point-of-care serological testing.We recently compared the performance of eight RDTs for dengue by using a panel of reference sera from patients with and without dengue who had been characterized previously by gold standard methods (1). Performance characteristics of the dengue RDTs were poor, with only one RDT considered potentially clinically informative. Here we present the results of a complementary prospective study undertaken in the Lao People's Democratic Republic (Laos) to determine the diagnostic performance characteristics of the same eight RDTs and to determine the tests' suitability for acute dengue viru...

Dengue: a continuing global threat

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Comparison of Two Generations of the Panbio Dengue NS1 Capture Enzyme-Linked Immunosorbent Assay

“…However, NS1 antigen capture tests have been recently used in many laboratories for early diagnosis of dengue (4,5,6,7,11,13,16). We evaluated the improvement of the NS1 antigen capture ELISA (Dengue Early ELISA) from Panbio compared to results previously obtained with the first-generation test (pan-E Early ELISA) (13).…”

Factors Influencing Dengue Virus Isolation by C6/36 Cell Culture and Mosquito Inoculation of Nested PCR-Positive Clinical Samples

“…With serial specimens, a 2-fold increase in IgG to dengue with an absolute value of ≥ 100 U indicated a secondary infection in the absence of anti-dengue IgM of ≥ 40 U. [22][23][24] Statistical analysis. Data were entered and manipulated using FoxPro for Windows software (Microsoft, Redmond, WA) and analyzed using SPSS for Windows version 12.0 (SPSS Inc., Chicago, IL) and SAS analytic software, version 9.1 (SAS Institute, Inc., Cary, NC).…”