Endemic Dengue In Indonesia: The Role of Candidate Antivirals And Immunomodulators on Clinical Outcomes and Immune Responses:

Endemic dengue in Indonesia remains a major public health challenge, with over 250,000 reported cases and more than 1,400 deaths in 2024, placing the country among the highest-burden nations in Southeast Asia. Clinical management is dominated by supportive care, and no specific antiviral agent is currently recommended for routine use in major guidelines. Recent advances in understanding dengue pathogenesis, particularly the interaction between viral replication and host immune responses, have stimulated development of candidate antivirals and immunomodulatory or platelet‑enhancing therapies aimed at reducing disease severity and mortality. This narrative review synthesises data from 1 January 2020 to 7 October 2025 on the effects of these interventions on clinical outcomes (duration of fever, length of hospital stay, progression to severe dengue, mortality) and immunological parameters (viremia, NS1 clearance, cytokine profiles, platelet indices), with emphasis on studies from endemic settings, including Indonesia. Electronic searches of major biomedical databases identified clinical trials, observational studies and preclinical studies reporting relevant outcomes. Overall, candidate antivirals such as celgosivir, ivermectin and newer niclosamide formulations show modest, inconsistent reductions in viremia without clear benefit in hard clinical endpoints. In contrast, several immunomodulators and platelet‑enhancing agents, including rupatadine, recombinant interleukin‑11, anti‑D, eltrombopag and Carica papaya preparations, demonstrate improved platelet counts and some surrogate outcomes, although evidence is heterogeneous and largely derived from small studies with non‑standardised endpoints. A recently proposed core outcome measurement set for dengue treatment trials provides a framework to harmonise outcome selection and assessment, and will be crucial for defining the future role of antivirals and immunomodulators in reducing the burden of endemic dengue.