Chikungunya virus infection: molecular biology, clinical characteristics, and epidemiology in Asian countries

Abstract

Chikungunya virus (CHIKV) is a re-emerging mosquito-borne human pathogen that causes chikungunya fever, which is typically accompanied by severe joint pain. In Asia, serological evidence indicated that CHIKV first emerged in 1954. From the 1950's to 2005, sporadic CHIKV infections were attributed to the Asian genotype. However, the massive outbreak of CHIKV in India and the Southwest Indian Ocean Islands in 2005 has since raised chikungunya as a worldwide public health concern. The virus is spreading globally, but mostly in tropical and subtropical regions, particularly in South and Southeast Asia. The emergence of the CHIKV East/Central/South African genotype-Indian Ocean lineage (ECSA-IOL) has caused large outbreaks in South and Southeast Asia affected more than a million people over a decade. Notably, the massive CHIKV outbreaks before 2016 and the more recent outbreak in Asia were driven by distinct ECSA lineages. The first significant CHIKV ECSA strains harbored the Aedes albopictus-adaptive mutation E1: A226V. More recently, another mass CHIKV ECSA outbreak in Asia started in India and spread beyond South and Southeast Asia to Kenya and Italy. This virus lacked the E1: A226V mutation but instead harbored two novel mutations (E1: K211E and E2: V264A) in an E1: 226A background, which enhanced its fitness in Aedes aegypti. The emergence of a novel ECSA strain may lead to a more widespread geographical distribution of CHIKV in the future. This review summarizes the current CHIKV situation in Asian countries and provides a general overview of the molecular virology, disease manifestation, diagnosis, prevalence, genotype distribution, evolutionary relationships, and epidemiology of CHIKV infection in Asian countries over the past 65 years. This knowledge is essential in guiding the epidemiological study, control, prevention of future CHIKV outbreaks, and the development of new vaccines and antivirals targeting CHIKV.

Keywords: Asia; Chikungunya virus; E1: K211E and E2: V264A; Novel ECSA; Outbreak.

Fig. 1

Geographical distribution of CHIKV lineages during 1952–2020 and that of its primary mosquito vectors. Different CHIKV lineages are represented by distinct colored symbols. The map also shows the distribution of the primary CHIKV mosquito vectors. Areas shown in pink indicate the range of Ae. aegypti, those shown in yellow indicate the range of Ae. albopictus, and the range of both primary vectors is indicated in orange. The range of both primary vectors was obtained from [16]. Distribution of chikungunya virus data were obtained from a number of studies [, –51]

Fig. 2

Historical timeline of major CHIKV outbreaks in Asia (1958–2020)

Fig. 3

Distribution and spread of the novel sub-lineage of CHIKV East/Central/South African (ECSA) genotype in South and Southeast Asia during 2015–2019. CHIKV Chikungunya virus, ECSA East/Central/South African genotype

Fig. 4

Evolutionary analysis of the complete genome of the CHIKV ECSA lineage. Bayesian time-scale tree of 169 genomes of the CHIKV ECSA lineage based on the strict clock model. The 95% HPD values of the most recent common ancestors (tMRC) are shown beside the nodes. The colored square of each strain corresponds to the amino acid mutations specific for the CHIKV ECSA lineage. CHIKV chikungunya virus, ECSA East/Central/South African, HPD highest posterior density

Fig. 5

Chikungunya cases in Thailand. a The number of chikungunya cases per year between 2008 and 2020. b The monthly number of chikungunya cases in Thailand between 2018 and 2020