High rate of subclinical Chikungunya virus infection and association of neutralizing antibody with protection in a prospective cohort in the Philippines

Autor(es): Yoon In-Kyu, Alera Maria Theresa, Lago Catherine B, Tac-An Ilya A, Villa Daisy, Fernandez Stefan, Thaisomboonsuk Butsaya, Klungthong Chonticha, Levy Jens W, Velasco John Mark, Roque Vito G, Salje Henrik, Macareo Louis R, Hermann Laura L, Nisalak Ananda, Srikiatkhachorn Anon


Resumo: Chikungunya virus (CHIKV) is a globally re-emerging arbovirus for which previous studies have indicated the majority of infections result in symptomatic febrile illness. We sought to characterize the proportion of subclinical - symptomatic CHIKV infections in a prospective cohort study in a country with known CHIKV circulation. A prospective longitudinal cohort of subjects ?6 months old underwent community-based active surveillance for acute febrile illness in Cebu City, Philippines from 2012-13. Subjects with fever history were clinically evaluated at acute, 2, 5, - 8 day visits, - at a 3-week convalescent visit. Blood was collected at the acute - 3-week convalescent visits. Symptomatic CHIKV infections were identified by positive CHIKV PCR in acute blood samples -/or CHIKV IgM/IgG ELISA seroconversion in paired acute/convalescent samples. Enrollment - 12-month blood samples underwent plaque reduction neutralization test (PRNT) using CHIKV attenuated strain 181/clone25. Subclinical CHIKV infections were identified by ?8-fold rise from a baseline enrollment PRNT titer <10 without symptomatic infection detected during the intervening surveillance period. Selected CHIKV PCR-positive samples underwent viral isolation - envelope protein-1 gene sequencing. Of 853 subjects who completed all study procedures at 12 months, 19 symptomatic infections (2.19 per 100 person-years) - 87 subclinical infections (10.03 per 100 person-years) occurred. The ratio of subclinical-to-symptomatic infections was 4.6:1 varying with age from 2:1 in 6 month-5 year olds to 12:1 in those >50 years old. Baseline CHIKV PRNT titer ?10 was associated with 100% (95%CI: 46.1, 100.0) protection from symptomatic CHIKV infection. Phylogenetic analysis demonstrated Asian genotype closely related to strains from Asia - the Caribbean. Subclinical infections accounted for a majority of total CHIKV infections. A positive baseline CHIKV PRNT titer was associated with protection from symptomatic CHIKV infection. These findings have implications for assessing disease burden, underst-ing virus transmission, - supporting vaccine development.


Imprenta: PLoS Neglected Tropical Diseases, v. 9, n. 5, p. e0003764, 2015


Identificador do objeto digital: 10.1371/journal.pntd.0003764


Descritores: Chikungunya virus - Arbovirus ; Chikungunya virus - Molecular structure ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - RNA ; Chikungunya virus - Antibodies ; Chikungunya virus - Infectious diseases ; Chikungunya virus - Serology ; Chikungunya virus - Viral infections ; Chikungunya virus - Serology ; Chikungunya Virus - Virus ; Chikungunya virus - Transmission ; Chikungunya virus - Vaccine ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Epidemiology ; Chikungunya virus - Immunology ; Chikungunya virus - Public health


Data de publicação: 2015