The Italian 2017 Outbreak Chikungunya Virus Belongs to an Emerging Aedes albopictus-Adapted Virus Cluster Introduced From the Indian Subcontinent.
ABSTRACT: Background:Chikungunya virus is an emerging mosquito-borne pathogen with a wide global distribution. With the severe morbidity that it causes, chikungunya virus is a major public health problem in the affected areas and poses a considerable risk for unaffected areas hosting competent vector populations. In the summer of 2017, Italy experienced a chikungunya virus outbreak that spread in the Lazio region and caused a secondary outbreak in the Calabrian village of Guardavalle, with a final case number of 436. The causative strain was recognized as an Indian Ocean lineage (IOL) virus. Methods:To understand the underlying genetic and molecular features of the outbreak virus, viruses from mosquito pools and clinical samples were isolated in cell culture and subjected to whole-genome sequencing and genetic analyses. Results:All 8 characterized genomes shared a high sequence identity. A distinct substitution pattern in the Italian 2017 viruses (including mutations in E1, E2, and nsP4) was partly shared with the Pakistani 2016 outbreak viruses. Evolutionary analyses indicate that these 2 recent outbreaks and several geographically widely distributed, travel-associated viruses form a cluster of rapidly emerging Indian-origin IOL viruses. Conclusions:Our analyses show that the 2017 Italian outbreak virus belongs to a cluster of novel IOL chikungunya viruses originating in India. Their emergence calls for enhanced monitoring and strengthened preparedness measures, including vector control programs and raised awareness among general practitioners in countries potentially at risk.
Project description:In recent decades, chikungunya virus (CHIKV) has become geographically widespread. In 2004, the CHIKV East/Central/South African (ECSA) genotype moved from Africa to Indian ocean islands and India followed by a large epidemic in Southeast Asia. In 2013, the CHIKV Asian genotype drove an outbreak in the Americas. Since 2016, CHIKV has re-emerged in the Indian subcontinent and Southeast Asia. In the present study, CHIKVs were obtained from Bangladesh in 2017 and Thailand in 2019, and their nearly full genomes were sequenced. Phylogenetic analysis revealed that the recent CHIKVs were of Indian Ocean Lineage (IOL) of genotype ECSA, similar to the previous outbreak. However, these CHIKVs were all clustered into a new distinct sub-lineage apart from the past IOL CHIKVs, and they lacked an alanine-to-valine substitution at position 226 of the E1 envelope glycoprotein, which enhances CHIKV replication in <i>Aedes albopictus</i>. Instead, all the re-emerged CHIKVs possessed mutations of lysine-to-glutamic acid at position 211 of E1 and valine-to-alanine at position 264 of E2. Molecular clock analysis suggested that the new sub-lineage CHIKV was introduced to Bangladesh around late 2015 and Thailand in early 2017. These results suggest that re-emerged CHIKVs have acquired different adaptations than the previous CHIKVs.
Project description: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.
Project description:Mosquito-borne virus infections, such as dengue and chikungunya, are continuously expanding their geographical range. The dengue virus, which is known to be a common cause of febrile illness in tropical areas of the Old World, is now widespread in the Americas. In most affected areas, all the four dengue virus serotypes have circulated. Recently, small clusters of dengue have been identified also in Southern Europe during the hot season. The chikungunya virus, initially restricted to Central Africa, where is a common cause of sporadic cases or small outbreaks, and Asia, where it is used to cause large epidemics, has recently invaded new territories. After ravaging Indian Ocean Islands and the Indian subcontinent, CHIKV caused an outbreak in north-eastern Italy. Recently, chikungunya has reached the Caribbean, causing for the first time a large epidemic on the American continent. Although Aedes aegypti is the main vector of both viruses, Aedes albopictus, the Asian 'Tiger' mosquito, is now playing an increasingly important role, contributing to their spread in temperate climate areas. Hereby, we focus the attention on outbreaks of dengue and chikungunya occurring in previously disease-free areas and discuss factors associated with the long-distance spread of the vector-borne infections, such as mutations increasing viral fitness, climate change, urbanization, and globalization of humans and vectors.
Project description:Following an outbreak of chikungunya virus (CHIKV) infections in Thailand in 2019, numerous cases of CHIKV infection have been diagnosed in Bangkok, the capital of the country. In our previous investigation of the vectors for disease transmission, we found natural infection of CHIKV in both male and female Aedes aegypti mosquitoes collected from the outbreak areas in Bangkok. Some reports mentioned the detection of CHIKV in Culex mosquitoes. In Thailand, the Culex quinquefasciatus Say mosquito is a common species found in urban and rural settings that coexists with Ae. aegypti. However, the role of Cx. quinquefasciatus mosquitoes in the spread of the Indian Ocean Lineage (IOL) of CHIKV in Thailand has never been investigated. In this study, Cx. quinquefasciatus were collected (16 males and 27 females) from an outbreak area in Bangkok. Eight of the 27 in field-caught female Cx. quinquefasciatus were positive for IOL CHIKV RNA, and 99-100% identity and full 100% coverage of sequences similar to CHIKV isolated from female Ae. aegypti in Bangkok, Thailand, whereas viral RNA was not detected in male samples using nested-RT-PCR. To determine whether CHIKV is able to replicate in Cx. quinquefasciatus, the laboratory strain of Cx. quinquefasciatus was allowed to feed on blood containing IOL CHIKV isolated from patient serum. The nested-RT-PCR, virus isolation, and immunofluorescence assay (IFA) were performed for CHIKV detection and replication. The results showed that CHIKV RNA was detected in Cx. quinquefasciatus until day 4 post infection. CHIKV did not produce any remarkable signs of infection, dissemination, or transmission in Cx. quinquefasciatus, and cytopathic effect (CPE) was not observed in C6/36 cells when infected with supernatant obtained from Cx. quinquefasciatus at days 7, 10, 14, and 21 post infection when compared to Ae. aegypti. The data from this study infer that CHIKV may be detected in Cx. quinquefasciatus but that the mosquito is not able to transmit CHIKV in Thailand.
Project description:Chikungunya virus is recognized as a serious public health problem. The complete genome was sequenced for a chikungunya virus isolated from the mosquito Aedes aegypti during a 2011 outbreak in Al Hodayda, Yemen, which resulted in significant human fatalities. Phylogenetic analysis demonstrated that this Yemeni isolate is most closely related to Indian Ocean strains of the east/central/south African genotype.
Project description:Chikungunya virus (CHIKV) is considered a public health problem due to its rapid spread and high morbidity. In 2016-2017 an outbreak of CHIKV was occurred in Pakistan but the data regarding the genomic diversity of CHIKV was not reported. Hence, the current study aimed to determine the genetic diversity of CHIKVs in Pakistan. A cross sectional study was carried out using sera of infected CHIKV patients (n = 1549) during the outbreak in Pakistan (2016-2018). Nucleotide sequencing of non-structural genes of CHIKV from eight isolates were performed followed by phylogenetic analysis using Bayesian method. Phylogenetic analysis suggested that the Pakistani CHIKV strains belonged to Indian Ocean Lineage (IOL) of genotype ECSA and C1.3a clade. Furthermore, the Pakistani isolates showed several key mutations (nsP2-H130Y, nsP2-E145D, nsP4-S55N and nsP4- R85G) corresponding to mutations reported in 2016 Indian strains of CHIKV. The molecular analysis revealed high evolutionary potential of CHIKV strains as well as better understanding of enhanced virulence and pathogenesis of this outbreak. The study highlights the need to continue surveillance in order to understand viral diversity over time and to devise preventive measures to limit diseases transmission in the region.
Project description:Local transmission of chikungunya, a debilitating mosquito-borne viral disease, was first reported in Singapore in January 2008. After 3 months of absence, locally acquired Chikungunya cases resurfaced in May 2008, causing an outbreak that resulted in a total of 231 cases by September 2008. The circulating viruses were related to East, Central, and South African genotypes that emerged in the Indian Ocean region in 2005. The first local outbreak was due to a wild-type virus (alanine at codon 226 of the envelope 1 gene) and occurred in an area where Aedes aegypti mosquitoes were the primary vector. Strains isolated during subsequent outbreaks showed alanine to valine substitution (A226V) and largely spread in areas predominated by Ae. albopictus mosquitoes. These findings led to a revision of the current vector control strategy in Singapore. This report highlights the use of entomologic and virologic data to assist in the control of chikungunya in disease-endemic areas.
Project description:Chikungunya viruses from the 2017 outbreak in Dhaka, Bangladesh, were analysed phylogenetically. E1 sequences from 21 strains belonged to the Indian Ocean clade of the East/Central/South African (ECSA) genotype, forming a novel cluster with latest South Asian strains. They lacked the A226V substitution.
Project description:We report a disease outbreak caused by chikungunya virus in Zhejiang Province, China, in August 2017. Phylogenic analysis indicated that this virus belonged to the Indian Ocean clade of the East/Central/South African genotype and was imported by a traveler returning from Bangladesh.
Project description:Chikungunya is repeatedly affecting Indonesia through successive outbreaks. The Asian genotype has been present in Asia since the late 1950s while the ECSA-IOL (East/Central/South Africa - Indian Ocean Lineage) genotype invaded Asia in 2005. In order to determine the extension of the circulation of the chikungunya virus (CHIKV) in Indonesia, mosquitoes were collected in 28 different sites from 12 Indonesian provinces in 2016-2017. The E1 subunit of the CHIKV envelope gene was sequenced while mosquitoes were genotyped using the mitochondrial <i>cox</i>1 (cytochrome C oxidase subunit 1) gene to determine whether a specific population was involved in the vectoring of CHIKV. A total of 37 CHIKV samples were found in 28 <i>Aedes aegypti</i>, 8 <i>Aedes albopictus</i> and 1 <i>Aedes butleri</i> out of 15,362 samples collected and tested. These viruses, like all Indonesian CHIKV since 2000, belonged to a genotype we propose to call the Asian-Pacific genotype. It also comprises the Yap isolates and viruses having emerged in Polynesia, the Caribbean and South America. They differ from the CHIKV of the Asian genotype found earlier in Indonesia indicating a replacement. These results raise the question of the mechanisms behind this fast and massive replacement.