Jessica E Manning1,2, Sophana Chea2,3, Daniel M Parker4, Jennifer A Bohl1, Sreyngim Lay2,3, Allyson Mateja5, Somnang Man2,3, Sreynik Nhek2,3, Aiyana Ponce1, Sokunthea Sreng2,3, Dara Kong2,3, Soun Kimsan3,6, Claudio Meneses1, Michael P Fay7, Seila Suon2,3, Rekol Huy3, Chanthap Lon1,2, Rithea Leang3,6, Fabiano Oliveira1. 1. Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. 2. International Center of Excellence in Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Phnom Penh, Cambodia. 3. National Center for Parasitology, Entomology, and Malaria Control, Ministry of Health, Phnom Penh, Cambodia. 4. University of California, Irvine, Irvine, California, USA. 5. Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA. 6. National Dengue Control Program, Ministry of Health, Phnom Penh, Cambodia. 7. Biostatistics Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Abstract
BACKGROUND: We established the first prospective cohort to understand how infection with dengue virus is influenced by vector-specific determinants such as humoral immunity to Aedes aegypti salivary proteins. METHODS: Children aged 2-9 years were 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 13 July to 30 August 2018, we enrolled 771 children. At baseline, 22% (173/770) had evidence of neutralizing antibodies to 1 or more dengue serotypes. By April 2020, 51 children had symptomatic dengue while 148 dengue-naive children had inapparent dengue defined by neutralization assays. In a multivariate model, individuals with higher antibodies to Ae. aegypti salivary proteins were 1.5 times more likely to have dengue infection (hazard ratio [HR], 1.47 [95% confidence interval {CI}, 1.05-2.06]; P = .02), particularly individuals with inapparent dengue (HR, 1.64 [95% CI, 1.12-2.41]; P = .01). CONCLUSIONS: High levels of seropositivity to Ae. aegypti salivary proteins are associated with future development of dengue infection, primarily inapparent, in dengue-naive Cambodian children. CLINICAL TRIALS REGISTRATION: NCT03534245. Published by Oxford University Press for the Infectious Diseases Society of America 2021.
BACKGROUND: We established the first prospective cohort to understand how infection with dengue virus is influenced by vector-specific determinants such as humoral immunity to Aedes aegypti salivary proteins. METHODS: Children aged 2-9 years were 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 13 July to 30 August 2018, we enrolled 771 children. At baseline, 22% (173/770) had evidence of neutralizing antibodies to 1 or more dengue serotypes. By April 2020, 51 children had symptomatic dengue while 148 dengue-naive children had inapparent dengue defined by neutralization assays. In a multivariate model, individuals with higher antibodies to Ae. aegypti salivary proteins were 1.5 times more likely to have dengue infection (hazard ratio [HR], 1.47 [95% confidence interval {CI}, 1.05-2.06]; P = .02), particularly individuals with inapparent dengue (HR, 1.64 [95% CI, 1.12-2.41]; P = .01). CONCLUSIONS: High levels of seropositivity to Ae. aegypti salivary proteins are associated with future development of dengue infection, primarily inapparent, in dengue-naive Cambodian children. CLINICAL TRIALS REGISTRATION: NCT03534245. Published by Oxford University Press for the Infectious Diseases Society of America 2021.
Authors: Berlin Londono-Renteria; Jenny C Cardenas; Lucio D Cardenas; Rebecca C Christofferson; Daniel M Chisenhall; Dawn M Wesson; Michael K McCracken; Daisy Carvajal; Christopher N Mores Journal: PLoS One Date: 2013-12-02 Impact factor: 3.240
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