Development of inapparent dengue associated with increased antibody levels to Aedes aegypti salivary proteins: a longitudinal dengue cohort in Cambodia.
BACKGROUND
We established the first prospective cohort to understand how infection with dengue virus is influenced by vector-specific determinants like humoral immunity to Aedes aegypti salivary proteins.


METHODS
Children aged two to nine years old enrolled in the PAGODAS (Pediatric Assessment Group of Dengue and Aedes Saliva) cohort with informed consent by their guardians. Children were followed semi-annually for antibodies to dengue and to proteins in Ae. aegypti salivary gland homogenate using enzyme-linked immunosorbent assays and dengue-specific neutralization titers. Children presented with fever at any time for dengue testing.


RESULTS
From July 13 to August 30, 2018, we enrolled 771 children. At baseline, 22% (173/770) had evidence of neutralizing antibodies to one or more dengue serotypes. By April 2020, 51 children had symptomatic dengue while 148 dengue-naïve children had inapparent dengue defined by neutralization assays. In a multivariate model, individuals with higher antibodies to Ae. aegypti salivary proteins were 1.5x more likely to have dengue infection (HR 1.47 95% CI 1.05-2.06; p=0.02), particularly individuals with inapparent dengue (HR 1.64 95% CI 1.12-2.41; p=0.01).


CONCLUSIONS
High levels of seropositivity to Ae. aegypti salivary proteins are associated with future development of dengue infection, primarily inapparent, in dengue-naïve Cambodian children.
['Manning|Jessica E|JE|0000-0003-0232-2196', 'Chea|Sophana|S|', 'Parker|Daniel M|DM|', 'Bohl|Jennifer A|JA|', 'Lay|Sreyngim|S|', 'Mateja|Allyson|A|', 'Man|Somnang|S|', 'Nhek|Sreynik|S|', 'Ponce|Aiyana|A|', 'Sreng|Sokunthea|S|', 'Kong|Dara|D|', 'Kimsan|Soun|S|', 'Meneses|Claudio|C|', 'Fay|Michael P|MP|', 'Suon|Seila|S|', 'Huy|Rekol|R|', 'Lon|Chanthap|C|', 'Leang|Rithea|R|', 'Oliveira|Fabiano|F|0000-0002-7924-8038']
dengue Aedes aegypti Cambodia mosquito saliva pediatric cohort