Sylvatic dengue virus type 4 in Aedes aegypti and Aedes albopictus mosquitoes in an urban setting in Peninsular Malaysia.

Dengue fever is endemic in Malaysia, contributing to significant economic and health burden in the country. Aedes aegypti and Ae. albopictus are the main vectors of the dengue virus (DENV), which circulates in sylvatic and human transmission cycles and has been present in Malaysia for decades. The study investigated the presence and distribution of DENV in urban localities in the Klang Valley, Peninsular Malaysia. A total of 364 Ae. aegypti and 1,025 Ae. albopictus larvae, and 10 Ae. aegypti and 42 Ae. albopictus adult mosquitoes were screened for the presence of DENV. In total, 31 (2.2%) samples were positive, of which 2 Ae. albopictus larvae were co-infected with two serotypes, one with DENV-2 and DENV-3 and the other with DENV-3 and DENV-4. Phylogenetic analysis determined that the isolates belonged to DENV-1 genotype I (1 Ae. aegypti adult), DENV-2 (1 Ae. albopictus larva), DENV-3 genotype V (3 Ae. aegypti larvae and 10 Ae. albopictus larvae) and DENV-4 genotype IV (6 Ae. aegypti larvae and 12 Ae. albopictus larvae), a sylvatic strain of DENV-4 which was most closely related with sylvatic strains isolated from arboreal mosquitoes and sentinel monkeys in Peninsular Malaysia in the 1970s. All four DENV serotypes were co-circulating throughout the study period. The detection of a sylvatic strain of DENV-4 in Ae. aegypti and Ae. albopictus mosquitoes in urban areas in Peninsular Malaysia highlights the susceptibility of these vectors to infection with sylvatic DENV. The infectivity and vector competence of these urban mosquitoes to this strain of the virus needs further investigation, as well as the possibility of the emergence of sylvatic virus into the human transmission cycle. Author summary Dengue is a mosquito-borne disease that has re-emerged as a major public health problem in the 21(st) Century. The four serotypes of dengue virus are capable of infecting humans with a range of symptoms and clinical outcomes, with the change in predominating serotypes often responsible for new dengue outbreaks. In this study, we surveyed urban sites in the Klang Valley, Malaysia, for Aedes aegypti and Aedes albopictus mosquito vectors and confirmed the presence of all four serotypes of the virus. We detected the presence of genotype V of dengue serotype 3, which has previously not been reported in the country, as well as a sylvatic strain of dengue serotype 4 that was closely related to strains obtained from forest-dwelling mosquito vectors and sentinel monkeys in Malaysia. The detection of a sylvatic strain of dengue virus in urban vectors raises questions over the risk of virus transmission to humans, especially with recent reports of severe clinical cases as a result of infection with sylvatic dengue virus serotypes. Further studies will be needed to determine the source and origins of these strains as well as the severity of dengue disease upon infection, especially with the development of new dengue vaccines.