Challenges and Opportunities of Laboratory diagnosis of Dengue virus infection: a review

Abstract

Background: Globally, dengue is one of the most important mosquito-borne viral diseases. Lack of effective vaccines and specific therapy against the disease threaten global health. Reliance on clinical diagnosis is complex due to clinical manifestations which resemble other diseases. This review examined various challenges of current dengue laboratory diagnoses, emerging technological opportunities and highlights considerations for future dengue diagnoses. Methods: A literature search from PubMed, Web of Science and Google Scholar databases was done from October 2018 to January 2019. Thematic descriptive analysis was done for all qualitative data and quantitative data analysis for computation of sensitivity and specificity of selected diagnostic tests at 95% confidence was done using R software (v3.4.4, mada package). The results: A total of 128 articles was reviewed. The current dengue laboratory diagnoses include (i) virus isolation (ii) detection of nucleic acid (iii) detection of non-structural protein 1(NS1) antigen and (iv) detection of anti-dengue antibodies. Assessment of diagnostic performance shows that reverse transcription-polymerase chain reaction (RT-PCR) and IgM antibody capture enzyme-linked immunosorbent assay (IgM ELISA) have high and consistent sensitivity (82.6% to 99.2% and 92.8% to 97.8%, respectively) and specificity (78.8% to 100% and 80.3% to 99%, respectively) compared to NS1 ELISA and NS1 commercial rapid tests with sensitivity (53.7% to 96.2% and 49.7% to 99.5%, respectively) and specificity (34.5% to 93.8% and 63.8% to 98.6%, respectively). Major challenges of dengue laboratory diagnosis include lack of reliable tests for routine purposes. Routine dengue tests are mainly serological, which are not suitable for discriminating dengue virus from other infecting flaviviruses due to cross-reactivity, narrow window of diagnosis due to short virus life cycle and inconsistent performance of commercial rapid tests. New technologies such as biosensors and nanobodies are being developed to improve sensitivity, specificity, detection time and reduce the cost. However, the performance of these new tools under field condition is unknown. Conclusion: Currently, RT-PCR and IgM ELISA are the most sensitive and specific dengue diagnostic tests, despite their limitations. Future research should explore emerging technologies to improve the sensitivity and specificity of dengue diagnostics.