Low Sensitivity of NS1 Protein Tests Evidenced during a Dengue Type 2 Virus Outbreak in Santos, Brazil, in 2010

Abstract

In 2010, a large outbreak of dengue occurred in Santos, Brazil. The detection of the NS1 antigen was used for diagnosis in addition to the detection of IgG, IgM, and RNA. A large number of NS1 false-negative results were obtained. A total of 379 RNA-positive samples were selected for thorough evaluation. NS1 was reactive in 37.7% of cases. Most of the cases were characterized as a secondary infection by dengue 2 virus. Sequencing of NS1 positive and negative isolates did not reveal any mutation that could justify the diagnostic failure. Use of existing NS1 tests in the Brazilian population may present a low negative predictive value, and they should be used with caution, preferentially after performing a validation with samples freshly obtained during the ongoing epidemic.

Evaluation of Commercially Available Assays for Diagnosis of Acute Dengue in Schoolchildren During an Epidemic Period in Medellin, Colombia

“…This is in agreement with the low sensitivity of NS1 detection observed during a dengue outbreak in 2010 in Santos, Brazil, where most of the infections were secondary infections and DENV-2 was the infecting serotype. 22 Sequencing analysis of the NS1 gene of these viruses did not reveal any mutation that could altered its reactivity with this diagnostic test. Low sensitivity (11.0%) was also reported when samples were drawn 4-5 days after the onset of symptoms.…”

“…Low sensitivity (11.0%) was also reported when samples were drawn 4-5 days after the onset of symptoms. 22 In other studies where NS1 antigen detection with SD Bioline Dengue Duo was compared with RT-PCR, the SD Bioline assay displayed better performances in specimens from patients with primary infections and when DENV-1 or DENV-3 were the infecting serotypes. 21,23 Guzman and others 8 also reported lower sensitivity of NS1 antigen detection in American countries (Nicaragua and Venezuela) compared with Asian countries.…”

“…8,21,26 Our results agree with others who reported that the combination of two or more diagnostic strategies is needed to improve the diagnostic accuracy of DENV infection. 8,[21][22][23]26 Combining direct DENV detection and antibody-based tests seems to be a particularly promising strategy. However, as seen in this study and evidenced by the low LR+ and LR− values, combinations of current assays do not guarantee the accuracy of the diagnosis when compared with standards such as PRNT or ELISPOT-MNT.…”

“…Several studies evidenced that the diagnostic performances of different dengue diagnosis kits vary depending on geographical and temporal factors. 8,22,24,27 Thus, validation of those kits in one country should take into account 1) the epidemiological settings (endemic, epidemic, and hyperepidemic periods), 2) the genetic background and immunological status of studied population, the different phases of the dengue disease, and 3) the DENV serotypes and genotypes that are circulating in the area.…”

NS1 Antigen Capture ELISA an Effective Method for Diagnosis of Early Dengue Infection - Report of an Outbreak at Angul District, Odisha, India

“…We detected maximum NS1Ag positivity (81.2%) in 1 to 5 days of fever. But low sensitivity of NS1 protein tests was evidenced during a dengue type 2 virus outbreak in Santos, Brazil, in 2010 [17]. Among the 92 subjects selected for IgM capture ELISA, only 47.1% were positive during 1 -5 days of fever.…”