Department of Medicine, Division of Infectious Diseases and Immunology
Immune System Diseases | Immunology of Infectious Disease | Infectious Disease | Virus Diseases
BACKGROUND: 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.
METHODS/FINDINGS: 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.
CONCLUSIONS: 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.
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DOI of Published Version
PLoS Negl Trop Dis. 2015 May 7;9(5):e0003764. doi: 10.1371/journal.pntd.0003764. eCollection 2015. Link to article on publisher's site
PLoS neglected tropical diseases
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. Jr.; Salje, Henrik; Macareo, Louis R.; Hermann, Laura L.; Nisalak, Ananda; and Srikiatkhachorn, Anon, "High rate of subclinical chikungunya virus infection and association of neutralizing antibody with protection in a prospective cohort in the Philippines" (2015). Open Access Articles. 2533.
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