Development of Inapparent Dengue Associated With Increased Antibody Levels to Aedes aegypti Salivary Proteins: A Longitudinal Dengue Cohort in Cambodia.

Jessica E Manning, Sophana Chea, Daniel M Parker, Jennifer A Bohl, Sreyngim Lay, Allyson Mateja, Somnang Man, Sreynik Nhek, Aiyana Ponce, Sokunthea Sreng, Dara Kong, Soun Kimsan, Claudio Meneses, Michael P Fay, Seila Suon, Rekol Huy, Chanthap Lon, Rithea Leang, Fabiano Oliveira
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引用次数: 5

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.

与埃及伊蚊唾液蛋白抗体水平升高相关的隐性登革热发展:柬埔寨登革热纵向队列研究
背景:我们建立了第一个前瞻性队列,以了解登革热病毒感染如何受到媒介特异性决定因素(如对埃及伊蚊唾液蛋白的体液免疫)的影响。方法:将2-9岁的儿童纳入PAGODAS(登革热和伊蚊唾液儿科评估组)队列,并征得其监护人的知情同意。每半年对儿童进行一次登革热抗体和伊蚊蛋白抗体检测。使用酶联免疫吸附试验和登革热特异性中和滴度对埃及伊蚊唾液腺进行匀浆。在任何时间出现发烧的儿童进行登革热检测。结果:2018年7月13日至8月30日,我们招募了771名儿童。基线时,22%(173/770)有一种或多种登革热血清型的中和抗体。到2020年4月,51名儿童出现登革热症状,148名登革热初发儿童通过中和试验确诊为隐性登革热。在一个多变量模型中,具有较高Ae抗体的个体。埃及伊蚊唾液蛋白感染登革热的可能性是其1.5倍(危险比[HR], 1.47[95%可信区间{CI}, 1.05-2.06];P = .02),尤其是隐性登革热患者(HR, 1.64 [95% CI, 1.12-2.41];p = 0.01)。结论:该地区伊蚊血清阳性。在未患登革热的柬埔寨儿童中,埃及伊蚊唾液蛋白与登革热感染的未来发展(主要是隐性的)有关。临床试验注册:NCT03534245。
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