Molecular Epidemiology, Evolution and Reemergence of Chikungunya Virus in South Asia

Abstract

Chikungunya virus (CHIKV) is a vector (mosquito)-transmitted alphavirus (family Togaviridae). CHIKV can cause fever and febrile illness associated with severe arthralgia and rash. Genotypic and phylogenetic analysis are important to understand the spread of CHIKV during epidemics and the diversity of circulating strains for the prediction of effective control measures. Molecular epidemiologic analysis of CHIKV is necessary to understand the complex interaction of vectors, hosts and environment that influences the genotypic evolution of epidemic strains. In this study, different works published during 1950s to 2020 concerning CHIKV evolution, epidemiology, vectors, phylogeny, and clinical outcomes were analyzed. Outbreaks of CHIKV have been reported from Bangladesh, Bhutan, India, Pakistan, Sri Lanka, Nepal, and Maldives in South Asia during 2007-2020. Three lineages- Asian, East/Central/South African (ECSA), and Indian Ocean Lineage (IOL) are circulating in South Asia. Lineage, ECSA and IOL became predominant over Asian lineage in South Asian countries during 2011-2020 epidemics. Further, the mutant E1-A226V is circulating in abundance with Aedes albopictus in India, Bangladesh, Nepal, and Bhutan. CHIKV is underestimated as clinical symptoms of CHIKV infection merges with the symptoms of dengue fever in South Asia. Failure to inhibit vector mediated transmission and predict epidemics of CHIKV increase the risk of larger global epidemics in future. To understand geographical spread of CHIKV, most of the studies focused on CHIKV outbreak, biology, pathogenesis, infection, transmission, and treatment. This updated study will reveal the collective epidemiology, evolution and phylogenies of CHIKV, supporting the necessity to investigate the circulating strains and vectors in South Asia.

Keywords: South Asia; chikungunya virus; epidemiology; evolution; phylogeny.

FIGURE 1

Map depicting worldwide distribution of chikungunya virus lineages during 1950s to 2020. Star signs indicate the first report/start of large outbreak of chikungunya virus. Circles indicate local outbreaks. (A) Red circles, arrows, and stars indicate ECSA lineage, black circles, arrows, and stars indicate West African lineage. (B) Navy blue circles, arrows, and stars indicate Asian lineage. (C) Brown circles, arrows, and stars indicate IOL lineage (Centers for Disease Control and Prevention (CDC), 2021; European Centre for Disease Prevention and Control (ECDC), 2021; Pan American and Health Organization (PAHO), 2021; World Health and Organization (WHO), 2021). The arrows indicated the probable spread of CHIKV based on the information extracted from Centers for Disease Control and Prevention (CDC), 2021; European Centre for Disease Prevention and Control (ECDC), 2021; Pan American and Health Organization (PAHO), 2021; World Health and Organization (WHO), 2021. Data were extracted directly from the databases and websites and cross-checked. The map was built using ArcGIS Pro software.

FIGURE 2

Onset of chikungunya virus outbreak in South Asia regions. (A) Indicates the case number of CHIKV patients during 1950s to 2003 in South Asia. (B) Indicates the case number of CHIKV patients during 2004 to 2020 in South Asian countries (Centers for Disease Control and Prevention (CDC), 2021; World Health and Organization (WHO), 2021). Star represents capital and large cities.

FIGURE 3

(A) Phylogenetic tree of globally distributed 1,066 genomes of chikungunya viruses sampled between February 1953 and December 2019. The phylogenetic tree was retrieved and from Nextstrain and modified based on the most updated information on CHIKV (de Bernardi Schneider et al., 2019; Spicher et al., 2021). (B) Phylogenetic tree of 157 whole genomes of CHIKV circulating in South Asia (India-88, Bangladesh-40, Sri Lanka-22, and Pakistan-7) sampled between February 1953 and December 2019. The trees were conducted using Maximum likelihood model. The trees were computed using bootstrap value of 1,000. Reference sequences were selected using temporal and spatial emergence of isolates during outbreaks in South Asia (de Bernardi Schneider et al., 2019; Spicher et al., 2021). (C) Mutational analysis of available reference genomes of CHIKV circulating in South Asian countries. The horizontal scale indicated the nucleotide base position in 5′ to 3′ direction, while the vertical scale indicated the number of substitutions per position in the genome (Nextstrain, 2021). Lineages are indicated as Asian urban (AUL), AUL-America (AUL-Am), South America (SAL), Middle Africa (MAL), Indian Ocean (IOL), East Africa (EAL), Africa and Asia (AAL), Sister Taxa to ECSA (sECSA), and West Africa (WA) (Nextstrain, 2021). Source: https://nextstrain.org/community/ViennaRNA/CHIKV.

FIGURE 4

Comparison of clinical manifestations of patients infected with CHIKV in South Asia and rest of the world (Centers for Disease Control and Prevention (CDC), 2021; European Centre for Disease Prevention and Control (ECDC), 2021; Pan American and Health Organization (PAHO), 2021; World Health and Organization (WHO), 2021).