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Open Access Highly Accessed Research article

Clinical features and pitfalls in the laboratory diagnosis of dengue in travellers

Ole Wichmann12*, Klaus Stark2, Pei-Yun Shu3, Matthias Niedrig2, Christina Frank2, Jyh-Hsiung Huang3 and Tomas Jelinek1

Author Affiliations

1 Berlin Institute of Tropical Medicine, Spandauer Damm 130, 14050 Berlin, Germany

2 Robert Koch Institute, Seestrasse 10, 13353 Berlin, Germany

3 Center for Research and Diagnostics, Center for Disease Control, Department of Health, 161 Kun-Yang Street, Taipei 115, Taiwan, Republic of China

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BMC Infectious Diseases 2006, 6:120  doi:10.1186/1471-2334-6-120

Published: 21 July 2006

Abstract

Background

Several enzyme-linked immunosorbent assay (ELISA)-kits are commercially available for the rapid diagnosis of dengue infection, and have demonstrated good sensitivity and specificity in paired serum samples. In practice, however, often only one blood sample is available from febrile travellers returning from dengue endemic areas.

Methods

To evaluate the diagnostic value of positive dengue antibody-titres performed by a standard ELISA (PanBio IgM- and IgG-ELISA) in single serum samples (regarded as "probable infection"), 127 positive samples were further analyzed using envelope/membrane IgM-, and nonstructural protein 1 IgM- and IgG-ELISAs, immunofluorescence assays, and real-time reverse transcription polymerase chain reaction assays (RT-PCR). A combination of the test-results served as the diagnostic "gold standard". A total of 1,035 febrile travellers returning from dengue-endemic countries with negative dengue-serology and RT-PCR served as controls to compare clinical and haematological features.

Results

Overall, only 64 (positive predictive value = 50%) of the probable cases were confirmed by additional analysis and 54 (42.5%) were confirmed to be "false-positive". Rash was the only clinical feature significantly associated with confirmed dengue fever. The combination of thrombocytopenia and leucopenia was present in 40.4% of confirmed and in 6.1% of false-positive cases. Thus, the positive predictive value for the combination of positive PanBio-ELISA plus the two haematological features was 90.5%.

Conclusion

The examination of paired serum samples is considered the most reliable serodiagnostic procedure for dengue. However, if only one blood sample is available, a single positive ELISA-result carries a high rate of false-positivity and should be confirmed using a second and more specific diagnostic technique. In the absence of further testing, platelet and white blood cell counts are helpful for the correct interpretation.