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

Abstract

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 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. Chikungunya virus (CHIKV) is a re-emerging mosquito-borne pathogen for which the majority of infections have been considered to result in febrile illness. We sought to characterize the proportion of subclinical and symptomatic CHIKV infections in a prospective cohort of subjects ≥6 months old who underwent active surveillance for acute febrile illness from 2012–13 in Cebu City, Philippines. Symptomatic CHIKV infections were detected by PCR and/or ELISA in acute/convalescent blood samples. Subclinical infections were identified by neutralizing antibody seroconversion between enrollment and 12-month visits without symptomatic infection. Among 853 subjects who completed all study activities at 12 months, 19 symptomatic and 87 subclinical infections occurred (2.19 and 10.03 per 100 person-years, respectively). A positive baseline CHIKV PRNT titer was associated with 100% (95%CI: 46.1, 100.0) protection from symptomatic infection. Phylogenetic analysis showed Asian genotype closely related to strains from the recent Caribbean epidemic. These findings can help to assess disease burden, understand virus transmission, and support vaccine development.