Effectiveness of antiviral, immunomodulatory and platelet-enhancing agents for treatment of dengue infection: A systematic review

Dengue is a vector-borne infectious disease, caused by dengue virus (DENV), with a rapidly increasing incidence worldwide. With no feasible, widely applicable prevention method available in the near term, the need for an effective treatment is of great importance. This systematic review aims to provide a comprehensive overview of potential antiviral, immunomodulatory, and platelet-enhancing therapies for the treatment of DENV. This systematic review was conducted according to the PRISMA guidelines. Clinical trials that investigate treatment options for DENV in the general population were included. Twenty-six studies were included, investigating length of hospital stay (<i>n</i> = 10), platelet count (<i>n</i> = 16), interleukin (IL)-6 levels (<i>n</i> = 4), virological log reduction (VLR) (<i>n</i> = 2), and non-structural (NS)-1 clearance time (<i>n</i> = 4). Focusing on potential antiviral agents, four studies showed a significant reduction regarding length of hospital stay, of which two used doxycycline. The most profound reduction of hospital stay was observed when doxycycline was combined with <i>Carica papaya</i> herbal extract (7.3 days vs 9.1 days). This combination was also able to achieve a significant rise in platelet count (+154.1 × 10⁹/L vs + 66.0 × 10⁹/L in 7 days). Immunomodulatory therapies did not demonstrate efficacy against DENV, although some evidence suggests that rupatadine may increase platelet count. The platelet-enhancing agents recombinant human IL-11, anti-rhD immunoglobulin (anti-D), and eltrombopag all showed a significant rise in platelet count. Small sample sizes make it challenging to draw definitive conclusions out of the included studies. Larger clinical trials are needed to evaluate treatments for DENV, with particular focus on doxycycline, <i>Carica papaya</i>, rupatadine, and platelet-enhancing agents.