High Rate of Subclinical Chikungunya Virus Infection and Association of Neutralizing Antibody with Protection in a Prospective Cohort in The Philippines

• Published in: PLoS neglected tropical diseases Vol. 9; no. 5; p. e0003764
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.05.2015; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Antibodies; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Antibodies, Viral - blood; Antibodies, Viral - immunology; Asia; Asymptomatic Infections - epidemiology; Base Sequence; Care and treatment; Caribbean Region; Chikungunya fever; Chikungunya Fever - epidemiology; Chikungunya Fever - immunology; Chikungunya Fever - transmission; Chikungunya Fever - virology; Chikungunya virus; Chikungunya virus - immunology; Chikungunya virus - isolation & purification; Child; Child, Preschool; Cohort Studies; Confidence intervals; Distribution; Enzyme-Linked Immunosorbent Assay; Female; Genotype; Genotype & phenotype; Health aspects; Humans; Illnesses; Immunoglobulin G - blood; Immunoglobulin M - blood; Infant; Infections; Longitudinal Studies; Male; Middle Aged; Mosquitoes; Neutralization Tests; Philippines - epidemiology; Phylogenetics; Phylogeny; Prospective Studies; Sequence Analysis, RNA; Studies; Surveillance; Young Adult; Asia; Philippines; Caribbean Region; ASW, Caribbean Sea; ISEW, Philippines
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0003764

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 and 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, and 8 day visits, and at a 3-week convalescent visit. Blood was collected at the acute and 3-week convalescent visits. Symptomatic CHIKV infections were identified by positive CHIKV PCR in acute blood samples and/or CHIKV IgM/IgG ELISA seroconversion in paired acute/convalescent samples. Enrollment and 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 and 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) and 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 and 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, understanding virus transmission, and supporting vaccine development.