Abstract
Background: As it is being witnessed by the rest of the world, Dengue virus (dengue/DENV) infection is the fastest spreading viral disease that happens to be transmitted by mosquitoes due to it registering 390 million cases annually and 3.9 billion people in 128 countries are infected. The clinical range between the asymptomatic infection and the life-threatening dengue hemorrhagic fever and shock syndrome should be diagnosed immediately with laboratory tests as the range will lead to the best treatment given to the patient, outbreak response and checks on the population health. This time variable viremia, antigenemia and host immune responses but the nature of diagnostic intervals to be too complex to be adequately represented in single-test and the potential of antigenically related flaviviruses co-circulating can be highly cross-reacting. The systematic review outlines the current molecular, antigen based and serological diagnostic systems with the view of coming up with an evidence-based recommendation to the care providers.
Methods: We choose the systematic literature search based on the PRISMA 2020 recommendations in the following databases: PubMed, Scopus, Web of Science, Cochrane Library, LILACS (January 2000 February 2025): 158 studies are included in it and they meet the following criteria: original research, which evaluates the performance of diagnostic tests in the conditions of the necessary reference standards and includes 50 or more participants. In QUADAS-2, there was two reviewers who participated in data extraction and quality determination.
Findings Molecular diagnostics has been reported to be the optimal on the first 5 days of illness with CDC Multiplex RT-PCR performing best in pooled sensitivity (98.5% 95% CI: 96.299.5) and specificity (100%). The sensitivity on day 7 however decreases to 45-60%. The best coverage occurs on day 3-7 with Platelia NS1 ELISA pooled sensitivity 84.5 (95) and specificity 98.2. They are also sensitivities, which vary considerably according to serotype (DENV-1: 92, DENV-4: 75), and that are reduced in a secondary infection (62.4% vs. 86.7% in primary, p<0.001). The rapid diagnostic tests were sensitive (19.2-99.1) with five out of the 18 products discovered by WHO having been found to be up to the minimum requirement. This peak sensitivity occurs in the days 4-7, day 8-14, which is the IgM sero-conversion (MAC-ELISA, 93.8). Cross-reaction of IgG with other flaviviruses (false positivity 2040%). There are some issues with the secondary infections: anamnester IgG reaction may be faster than the IgM (IgM not detected in 2030%), and the sensitivity of NS1 is significantly lesser. The reason behind this is that the multi-platform based diagnostic algorithms that is founded on illness specific ileal day is more productive in terms of diagnostic (25-35 percent) than single-test based. Recommendation: Dengue diagnosis is recommended to be done using dynamic and phase specific testing methods that will involve the application of both the molecular, antigenic and serological tests. It should be done with the help of molecular tests and NS1 antigen during the first 5-7 days followed by IgM serology. However, all the tests are not sufficient to address the entire disease pathology. Dengue geographical distribution coupled with co-circulation with other flaviviruses may confound the diagnosis with a false positive of up to 40 percent in the multi-flavivirus regions. Reference laboratory capability has been needed to do conferential testing on PRNT, although more modern multiplex molecular tests (BioFire FilmArray, QIAstat-Dx) can be employed to identify dengue, chikungunya and Zika with concordance similar to 95-98. The Nanotechnological biosensors and DETECTR (CRISPR-based diagnostics) are already showing good results. The health workers are expected to be knowledgeable about the temporal dynamics of the diagnosis so that they could conduct the necessary number of tests and further examine results in order to make the needed decision of tests. Qualitative diagnostics and standard algorithms are another valuable choice of investment that will reduce the morbidity and death rates related to dengue.