Insect-Specific Flaviviruses: Novel Strategies for Indonesian Vector-Borne Disease Control.

Arboviral diseases in Indonesia remain a public health problem and a threat. The annual increase in cases is caused by changes in bioclimatological factors, increased reports of resistance to insecticides and larvicides, and low community participation in vector control, resulting in an uncontrolled abundance of the species. Therefore, an alternative, safe, effective, and evidence-based vector control approach is needed. This narrative review, conducted via the SANRA protocol encompassing PubMed, Scopus, and Web of Science (2014-2024), aims to (1) synthesize current Insect-Specific Flavivirus (ISF) biology, classification, and distribution with emphasis on Indonesia and Southeast Asia; (2) evaluate evidence for ISF-mediated interference with pathogenic flavivirus transmission; (3) compare ISF with Wolbachia-based biocontrol strategies; and (4) identify research priorities and implementation considerations for ISF-based vector control in Indonesia. Eleven articles were further analyzed. Three ISF species ( cell-fusion agent virus , Culex flavivirus , and Aedes flavivirus ) have been detected in Indonesian mosquito populations. Experimental studies have shown that Nhumirim virus reduces Zika transmission, whereas Palm Creek virus suppresses West Nile virus replication. The Binjari virus -based chimeric vaccine platform produced a good prevention and control model; however, the varying vertical transmission of ISF, lack of field validation, and absence of a regulatory framework are barriers to implementation. However, ISF still requires optimization of population persistence and the development of large-scale application methods. Research priorities include field effectiveness validation, characterization of ISF interactions, and development of standardized release protocols for the translation of ISF technology as a complement to integrated vector control in Indonesia.