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1.
Viruses ; 16(6)2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38932218

ABSTRACT

Chikungunya virus (CHIKV) is transmitted by mosquito bites and causes chikungunya fever (CHIKF). CHIKV has a single-stranded RNA genome and belongs to a single serotype with three genotypes. The Asian lineage has recently emerged in the Western Hemisphere, likely due to travel-associated introduction. Genetic variation accumulates in the CHIKV genome as the virus replicates, creating new lineages. Whole genome sequencing is ideal for studying virus evolution and spread but is expensive and complex. This study investigated whether specific, highly variable regions of the CHIKV genome could recapitulate the phylogeny obtained with a complete coding sequence (CDS). Our results revealed that concatenated highly variable regions accurately reconstructed CHIKV phylogeny, exhibiting statistically indistinguishable branch lengths and tree confidence compared to CDS. In addition, these regions adequately inferred the evolutionary relationships among CHIKV isolates from the American outbreak with similar results to the CDS. This finding suggests that highly variable regions can effectively capture the evolutionary relationships among CHIKV isolates, offering a simpler approach for future studies. This approach could be particularly valuable for large-scale surveillance efforts.


Subject(s)
Chikungunya Fever , Chikungunya virus , Genetic Variation , Genome, Viral , Phylogeny , Chikungunya virus/genetics , Chikungunya virus/classification , Chikungunya virus/isolation & purification , Chikungunya Fever/virology , Humans , Genotype , Whole Genome Sequencing/methods , Evolution, Molecular , Genomics/methods , Open Reading Frames , Animals , RNA, Viral/genetics
2.
Virol J ; 21(1): 141, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38902719

ABSTRACT

BACKGROUND: Despite dengue virus (DENV) outbreak in Gabon a decade ago, less is known on the potential circulation of DENV serotypes in the country. Previous studies conducted in some areas of the country, are limited to hospital-based surveys which reported the presence of some cases of serotype 2 and 3 seven years ago and more recently the serotype 1. As further investigation, we extend the survey to the community of Moyen Ogooué region with the aim to assess the presence of the dengue virus serotypes, additionally to characterize chikungunya (CHIKV) infection and describe the symptomatology associated with infections. METHOD: A cross-sectional survey was conducted from April 2020 to March 2021. The study included participants of both sexes and any age one year and above, with fever or history of fever in the past seven days until blood collection. Eligible volunteers were clinically examined, and blood sample was collected for the detection of DENV and CHIKV using RT-qPCR. Positive samples were selected for the target sequencing. RESULTS: A total of 579 volunteers were included. Their mean age (SD) was 20 (20) years with 55% of them being female. Four cases of DENV infection were diagnosed giving a prevalence of 0.7% (95%CI: 0.2-1.8) in our cohort while no case of CHIKV was detected. The common symptoms and signs presented by the DENV cases included fatigue, arthralgia myalgia, cough, and loss of appetite. DENV-1was the only virus detected by RT-qPCR. CONCLUSION: Our results confirm the presence of active dengue infection in the region, particularly DENV-1, and could suggest the decline of DENV-2 and DENV-3. Continuous surveillance remains paramount to comprehensively describe the extent of dengue serotypes distribution in the Moyen-Ogooué region of Gabon.


Subject(s)
Dengue Virus , Dengue , Serogroup , Humans , Gabon/epidemiology , Dengue Virus/genetics , Dengue Virus/classification , Dengue Virus/isolation & purification , Female , Male , Dengue/epidemiology , Dengue/virology , Cross-Sectional Studies , Adult , Young Adult , Adolescent , Child, Preschool , Child , Middle Aged , Infant , Chikungunya Fever/epidemiology , Chikungunya Fever/virology , Aged , Prevalence , Chikungunya virus/genetics , Chikungunya virus/classification , Chikungunya virus/isolation & purification
3.
Emerg Microbes Infect ; 13(1): 2362941, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38813649

ABSTRACT

Chikungunya virus (CHIKV) has emerged as a significant public health concern due to its rapid spread and potential for causing debilitating epidemics. In Argentina, the virus has garnered attention since its introduction to the Americas in 2013, due to its growing incidence and impact in neighbouring countries. Here we present a comprehensive analysis of the spatiotemporal dynamics of CHIKV in Argentina, focusing on the evolutionary trajectory of its genetic variants. Through a combination of active surveillance, screening of historical and recent samples, and whole-genome sequencing, we traced the evolutionary history of CHIKV lineages circulating within the country. Our results reveal that two distinct genotypes circulated in Argentina: The Asian lineage during the 2016 epidemic and the ECSA lineage in 2023. This distribution reflects the dominance of particular variants across Latin America. Since 2023, the ECSA lineage has led to a surge in cases throughout the Americas, marking a significant shift. The replacement of lineages in the American region constitutes a major epidemiological event, potentially affecting the dynamics of virus transmission and the clinical outcomes in impacted populations. The spatiotemporal analysis highlights CHIKV's distribution across Argentina and underscores the significant role of human mobility, especially when considering recent epidemics in neighbouring countries such as Paraguay and Uruguay, which have facilitated the spread and introduction of the viral strain into different districts. By integrating epidemiological data with genomic insights, we elucidate the patterns of virus dissemination, highlighting key areas of transmission and potential factors contributing to its spread.


Subject(s)
Chikungunya Fever , Chikungunya virus , Evolution, Molecular , Genotype , Phylogeny , Argentina/epidemiology , Chikungunya virus/genetics , Chikungunya virus/classification , Chikungunya virus/isolation & purification , Chikungunya Fever/epidemiology , Chikungunya Fever/virology , Chikungunya Fever/transmission , Humans , Genome, Viral , Latin America/epidemiology , Whole Genome Sequencing , Spatio-Temporal Analysis , Genetic Variation
4.
Viruses ; 16(5)2024 04 29.
Article in English | MEDLINE | ID: mdl-38793584

ABSTRACT

Genetic studies preceded by the observation of an unknown mosquito species in Mikolów (Poland) confirmed that it belongs to a new invasive species in Polish fauna, Aedes japonicus (Theobald, 1901), a known vector for numerous infectious diseases. Ae. japonicus is expanding its geographical presence, raising concerns about potential disease transmission given its vector competence for chikungunya virus, dengue virus, West Nile virus, and Zika virus. This first genetically confirmed identification of Ae. japonicus in Poland initiates a comprehensive review of the literature on Ae. japonicus, its biology and ecology, and the viral infections transmitted by this species. This paper also presents the circumstances of the observation of Ae. japonicus in Poland and a methodology for identifying this species.


Subject(s)
Aedes , Mosquito Vectors , Poland , Aedes/virology , Animals , Mosquito Vectors/virology , Introduced Species , Humans , West Nile virus/genetics , Dengue Virus/genetics , Dengue Virus/isolation & purification , Dengue Virus/classification , Zika Virus/genetics , Chikungunya virus/genetics , Chikungunya virus/classification , Chikungunya virus/isolation & purification
5.
J Vector Borne Dis ; 61(1): 61-71, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38648407

ABSTRACT

BACKGROUND OBJECTIVES: Dengue and chikungunya infections are one of the major health problems that have plagued the human population globally. All dengue virus (DENV) serotypes circulate within Malaysia with particular serotypes dominating in different years/outbreaks. In the state of Kelantan, an increasing number of DENV and chikungunya virus (CHIKV) new cases have been reported, including several deaths. This study aimed to isolate and detect these arboviruses from adult mosquitoes in Kelantan. METHODS: Adult mo squito samples were collected from January to August 2019 and were identified according to gender, species and locality. The isolation of the virus was done in C6/36 cells. Dengue NS1 antigen was carried out using direct mosquito lysate and mosquito culture supernatant. Detection and serotyping of the DENV was performed using multiplex RT-PCR and CHIKV detection using a one-step RT-PCR assay. RESULTS: Of 91 mosquito pools, four were positive for NS1 antigen comprising two pools (2.2%) of male Ae. albopictus (Pulau Melaka and Kubang Siput) and two pools (2.2%) of Ae. aegypti (Kampung Demit Sungai). DENV 1 was detected in one pool (0.9%) of female Ae. albopictus among 114 tested Aedes pools. Two pools of 114 pools (1.7%) from both male Aedes species were positive with double serotypes, DENV 1 and DENV 2 (Pulau Melaka). However, no pool was positive for CHIKV. INTERPRETATION CONCLUSION: The presence of DENV and the main vectors of arboviruses in Kelantan are pertinent indicators of the need to improve vector controls to reduce arbovirus infections among people in the localities.


Subject(s)
Aedes , Chikungunya virus , Dengue Virus , Dengue , Mosquito Vectors , Animals , Malaysia , Dengue Virus/genetics , Dengue Virus/isolation & purification , Dengue Virus/classification , Chikungunya virus/genetics , Chikungunya virus/isolation & purification , Chikungunya virus/classification , Male , Female , Aedes/virology , Mosquito Vectors/virology , Dengue/virology , Chikungunya Fever/virology , Humans , Viral Nonstructural Proteins/genetics , Serogroup
6.
Viruses ; 16(4)2024 04 09.
Article in English | MEDLINE | ID: mdl-38675917

ABSTRACT

The incidence of chikungunya has dramatically surged worldwide in recent decades, imposing an expanding burden on public health. In recent years, South America, particularly Brazil, has experienced outbreaks that have ravaged populations following the rapid dissemination of the chikungunya virus (CHIKV), which was first detected in 2014. The primary vector for CHIKV transmission is the urban mosquito species Aedes aegypti, which is highly prevalent throughout Brazil. However, the impact of the locally circulating CHIKV genotypes and specific combinations of local mosquito populations on vector competence remains unexplored. Here, we experimentally analyzed and compared the infectivity and transmissibility of the CHIKV-ECSA lineage recently isolated in Brazil among four Ae. aegypti populations collected from different regions of the country. When exposed to CHIKV-infected AG129 mice for blood feeding, all the mosquito populations displayed high infection rates and dissemination efficiency. Furthermore, we observed that all the populations were highly efficient in transmitting CHIKV to a vertebrate host (naïve AG129 mice) as early as eight days post-infection. These results demonstrate the high capacity of Brazilian Ae. aegypti populations to transmit the locally circulating CHIKV-ECSA lineage. This observation could help to explain the high prevalence of the CHIKV-ECSA lineage over the Asian lineage, which was also detected in Brazil in 2014. However, further studies comparing both lineages are necessary to gain a better understanding of the vector's importance in the epidemiology of CHIKV in the Americas.


Subject(s)
Aedes , Chikungunya Fever , Chikungunya virus , Mosquito Vectors , Animals , Aedes/virology , Chikungunya virus/genetics , Chikungunya virus/classification , Chikungunya virus/physiology , Chikungunya virus/isolation & purification , Brazil/epidemiology , Chikungunya Fever/transmission , Chikungunya Fever/virology , Chikungunya Fever/epidemiology , Mice , Mosquito Vectors/virology , Genotype , Female , Phylogeny
7.
Viruses ; 16(4)2024 04 19.
Article in English | MEDLINE | ID: mdl-38675976

ABSTRACT

RNA viruses quickly evolve subtle genotypic changes that can have major impacts on viral fitness and host range, with potential consequences for human health. It is therefore important to understand the evolutionary fitness of novel viral variants relative to well-studied genotypes of epidemic viruses. Competition assays are an effective and rigorous system with which to assess the relative fitness of viral genotypes. However, it is challenging to quickly and cheaply distinguish and quantify fitness differences between very similar viral genotypes. Here, we describe a protocol for using reverse transcription PCR in combination with commercial nanopore sequencing services to perform competition assays on untagged RNA viruses. Our assay, called the Universal Competition Assay by Nanopore Sequencing (U-CAN-seq), is relatively cheap and highly sensitive. We used a well-studied N24A mutation in the chikungunya virus (CHIKV) nsp3 gene to confirm that we could detect a competitive disadvantage using U-CAN-seq. We also used this approach to show that mutations to the CHIKV 5' conserved sequence element that disrupt sequence but not structure did not affect the fitness of CHIKV. However, similar mutations to an adjacent CHIKV stem loop (SL3) did cause a fitness disadvantage compared to wild-type CHIKV, suggesting that structure-independent, primary sequence determinants in this loop play an important role in CHIKV biology. Our novel findings illustrate the utility of the U-CAN-seq competition assay.


Subject(s)
Chikungunya virus , Mutation , Nanopore Sequencing , Nanopore Sequencing/methods , Chikungunya virus/genetics , Chikungunya virus/classification , Humans , Genotype , Genetic Fitness , RNA, Viral/genetics , Animals , RNA Viruses/genetics , RNA Viruses/classification , Chikungunya Fever/virology
8.
PLoS One ; 16(12): e0260424, 2021.
Article in English | MEDLINE | ID: mdl-34941888

ABSTRACT

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.


Subject(s)
Chikungunya Fever/epidemiology , Chikungunya Fever/virology , Chikungunya virus/isolation & purification , Viral Nonstructural Proteins/genetics , Amino Acid Substitution , Chikungunya virus/classification , Chikungunya virus/genetics , Cross-Sectional Studies , Genome, Viral , Genotype , Humans , Pakistan/epidemiology , Phylogeny
9.
mBio ; 12(6): e0273821, 2021 12 21.
Article in English | MEDLINE | ID: mdl-34749526

ABSTRACT

Previous studies have shown that the adaptation of Indian Ocean lineage (IOL) chikungunya virus (CHIKV) strains for Aedes albopictus transmission was mediated by an E1-A226V substitution, followed by either a single substitution in E2 or synergistic substitutions in the E2 and E3 envelope glycoproteins. Here, we examined whether Asian lineage strains, including those that descended from the 2014 Caribbean introduction, are likely to acquire these A. albopictus-adaptive E2 substitutions. Because Asian lineage strains cannot adapt through the E1-A226V substitution due to an epistatic constraint, we first determined that the beneficial effect of these E2 mutations in IOL strains is independent of E1-A226V. We then introduced each of these E2 adaptive mutations into the Asian lineage backbone to determine if they improve infectivity for A. albopictus. Surprisingly, our results indicated that in the Asian lineage backbone, these E2 mutations significantly decreased CHIKV fitness in A. albopictus. Furthermore, we tested the effects of these mutations in Aedes aegypti and observed different results from those in A. albopictus, suggesting that mosquito species-specific factors that interact with the envelope proteins are involved in vector infection efficiency. Overall, our results indicate that the divergence between Asian lineage and IOL CHIKVs has led them onto different adaptive landscapes with differing potentials to expand their vector host range. IMPORTANCE Since its introduction into the Caribbean in October 2013, CHIKV has rapidly spread to almost the entire neotropical region. However, its potential to further spread globally, including into more temperate climates, depends in part on its ability to be transmitted efficiently by Aedes albopictus, which can survive colder winters than A. aegypti. We examined in an Asian lineage backbone A. albopictus-adaptive mutations that arose from 2005 to 2009 in Indian Ocean lineage (IOL) strains. Our results predict that the Asian CHIKV lineage now in the Americas will not readily adapt for enhanced A. albopictus transmission via the same mechanisms or adaptive mutations used previously by IOL strains. The vector species- and CHIKV lineage-specific effects caused by adaptive CHIKV envelope glycoprotein substitutions may elucidate our understanding of the mechanisms of mosquito infection and spread.


Subject(s)
Chikungunya virus/classification , Chikungunya virus/genetics , Mosquito Vectors/virology , Adaptation, Physiological , Aedes/physiology , Aedes/virology , Amino Acid Substitution , Animals , Chikungunya virus/physiology , Evolution, Molecular , Mosquito Vectors/physiology , Mutation , Phylogeny , Species Specificity , Viral Envelope Proteins/genetics
10.
Arch Virol ; 166(10): 2895-2899, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34351521

ABSTRACT

After the 2005-2009 chikungunya epidemic, intermittent outbreaks were reported in many parts of India. The outbreaks were caused by either locally circulating strains or imported viruses. Virus transmission routes can be traced by complete genome sequencing studies. We investigated two outbreaks in 2014 and 2019 in Kerala, India. Chikungunya virus (CHIKV) was isolated from the samples, and whole genomes were sequenced for a 2014 isolate and a 2019 isolate. Phylogenetic analysis revealed that the isolates formed a separate group with a 2019 isolate from Pune, Maharashtra, and belonged to the East/Central/South African (ECSA) genotype, Indian subcontinent sublineage of the Indian Ocean Lineage (IOL). A novel mutation at amino acid position 76 of the E2 gene was observed in the group. The phylogenetic results suggest that the outbreaks might have been caused by a virus that had been circulating in India since 2014. A detailed study is needed to investigate the evolution of CHIKV in India.


Subject(s)
Chikungunya Fever/epidemiology , Chikungunya Fever/virology , Chikungunya virus/genetics , Disease Outbreaks , Chikungunya Fever/transmission , Chikungunya virus/classification , Chikungunya virus/isolation & purification , Genome, Viral/genetics , Genotype , Humans , India/epidemiology , Mutation , Phylogeny , RNA, Viral/genetics , Viral Envelope Proteins/genetics
11.
Nat Commun ; 12(1): 4636, 2021 07 30.
Article in English | MEDLINE | ID: mdl-34330906

ABSTRACT

Chikungunya virus (CHIKV) is a reemerging mosquito-borne virus that causes swift outbreaks. Major concerns are the persistent and disabling polyarthralgia in infected individuals. Here we present the results from a first-in-human trial of the candidate simian adenovirus vectored vaccine ChAdOx1 Chik, expressing the CHIKV full-length structural polyprotein (Capsid, E3, E2, 6k and E1). 24 adult healthy volunteers aged 18-50 years, were recruited in a dose escalation, open-label, nonrandomized and uncontrolled phase 1 trial (registry NCT03590392). Participants received a single intramuscular injection of ChAdOx1 Chik at one of the three preestablished dosages and were followed-up for 6 months. The primary objective was to assess safety and tolerability of ChAdOx1 Chik. The secondary objective was to assess the humoral and cellular immunogenicity. ChAdOx1 Chik was safe at all doses tested with no serious adverse reactions reported. The vast majority of solicited adverse events were mild or moderate, and self-limiting in nature. A single dose induced IgG and T-cell responses against the CHIKV structural antigens. Broadly neutralizing antibodies against the four CHIKV lineages were found in all participants and as early as 2 weeks after vaccination. In summary, ChAdOx1 Chik showed excellent safety, tolerability and 100% PRNT50 seroconversion after a single dose.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Chikungunya Fever/immunology , Chikungunya virus/immunology , Viral Vaccines/immunology , Adolescent , Adult , Chikungunya Fever/prevention & control , Chikungunya Fever/virology , Chikungunya virus/classification , Chikungunya virus/physiology , Cytokines/immunology , Cytokines/metabolism , Enzyme-Linked Immunosorbent Assay , Fatigue/chemically induced , Female , Headache/chemically induced , Humans , Immunoglobulin G/immunology , Injections, Intramuscular , Male , Middle Aged , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Vaccination/methods , Viral Vaccines/administration & dosage , Viral Vaccines/adverse effects , Young Adult
12.
PLoS One ; 16(3): e0247314, 2021.
Article in English | MEDLINE | ID: mdl-33690657

ABSTRACT

Between 2018 and 2019, the incidence of chikungunya was approximately 15,000 cases across 60 provinces in Thailand. Here, the clinical presentations in chikungunya, emergent pattern, and genomic diversity of the chikungunya virus (CHIKV) causing this massive outbreak were demonstrated. A total of 1,806 sera samples from suspected cases of chikungunya were collected from 13 provinces in Thailand, and samples were tested for the presence of CHIKV RNA, IgG, and IgM using real-time PCR, enzyme-linked immunoassay (ELISA), commercial immunoassay (rapid test). The phylogenetic tree of CHIKV whole-genome and CHIKV E1 were constructed using the maximum-likelihood method. CHIKV infection was confirmed in 547 (42.2%) male and 748 (57.8%) female patients by positive real-time PCR results and/or CHIKV IgM antibody titers. Unsurprisingly, CHIKV RNA was detected in >80% of confirmed cases between 1 and 5 days after symptom onset, whereas anti-CHIKV IgM was detectable in >90% of cases after day 6. Older age was clearly one of the risk factors for the development of arthralgia in infected patients. Although phylogenetic analysis revealed that the present CHIKV Thailand strain of 2018-2020 belongs to the East, Central, and Southern African (ECSA) genotype similar to the CHIKV strains that caused outbreaks during 2008-2009 and 2013, all present CHIKV Thailand strains were clustered within the recent CHIKV strain that caused an outbreak in South Asia. Interestingly, all present CHIKV Thailand strains possess two mutations, E1-K211E, and E2-V264A, in the background of E1-226A. These mutations are reported to be associated with virus-adapted Aedes aegypti. Taken together, it was likely that the present CHIKV outbreak in Thailand occurred as a result of the importation of the CHIKV strain from South Asia. Understanding with viral genetic diversity is essential for epidemiological study and may contribute to better disease management and preventive measures.


Subject(s)
Antibodies, Viral/blood , Chikungunya Fever/epidemiology , Chikungunya virus/classification , Mutation , RNA, Viral/genetics , Adolescent , Adult , Age Factors , Aged , Chikungunya Fever/blood , Chikungunya Fever/virology , Chikungunya virus/genetics , Chikungunya virus/immunology , Child , Child, Preschool , Disease Outbreaks , Female , Genotype , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Infant , Likelihood Functions , Male , Middle Aged , Phylogeny , Thailand/epidemiology , Whole Genome Sequencing , Young Adult
13.
Arch Virol ; 166(5): 1455-1462, 2021 May.
Article in English | MEDLINE | ID: mdl-33704558

ABSTRACT

During the dengue epidemic in Yunnan Province, China, during 2019, a concurrent outbreak of chikungunya occurred in the city of Ruili, which is located in the southwest of the province, adjacent to Myanmar. As part of this outbreak, three neonatal cases of infection with indigenous chikungunya virus from mother-to-child (vertical) transmission were observed. Isolates of chikungunya virus were obtained from 37 serum samples of patients with chikungunya during this outbreak, and a phylogenetic analysis of these isolates revealed that they belong to the Indian Ocean subclade of the East/Central/South African genotype. The E1 genes of these viruses did not harbor the A226V mutation.


Subject(s)
Chikungunya Fever/virology , Chikungunya virus/isolation & purification , Communicable Diseases, Emerging/virology , Infectious Disease Transmission, Vertical , Chikungunya Fever/epidemiology , Chikungunya Fever/transmission , Chikungunya virus/classification , Chikungunya virus/genetics , China/epidemiology , Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/transmission , Disease Outbreaks , Female , Genome, Viral/genetics , Genotype , Humans , Male , Mutation , Phylogeny , RNA, Viral/genetics , Viral Proteins/genetics
14.
BMC Infect Dis ; 21(1): 186, 2021 Feb 18.
Article in English | MEDLINE | ID: mdl-33602147

ABSTRACT

BACKGROUND: Chikungunya fever (CHIKF) was first described in Tanzania in 1952. Several epidemics including East Africa have occurred, but there are no descriptions of longitudinal surveillance of endemic disease. Here, we estimate the incidence of CHIKF in coastal Kenya and describe the associated viral phylogeny. METHODS: We monitored acute febrile illnesses among 3500 children visiting two primary healthcare facilities in coastal Kenya over a 5-year period (2014-2018). Episodes were linked to a demographic surveillance system and blood samples obtained. Cross-sectional sampling in a community survey of a different group of 435 asymptomatic children in the same study location was done in 2016. Reverse-transcriptase PCR was used for chikungunya virus (CHIKV) screening, and viral genomes sequenced for phylogenetic analyses. RESULTS: We found CHIKF to be endemic in this setting, associated with 12.7% (95% CI 11.60, 13.80) of all febrile presentations to primary healthcare. The prevalence of CHIKV infections among asymptomatic children in the community survey was 0.7% (95% CI 0.22, 2.12). CHIKF incidence among children < 1 year of age was 1190 cases/100,000-person years and 63 cases/100,000-person years among children aged ≥10 years. Recurrent CHIKF episodes, associated with fever and viraemia, were observed among 19 of 170 children with multiple febrile episodes during the study period. All sequenced viral genomes mapped to the ECSA genotype albeit distinct from CHIKV strains associated with the 2004 East African epidemic. CONCLUSIONS: CHIKF may be a substantial public health burden in primary healthcare on the East African coast outside epidemic years, and recurrent infections are common.


Subject(s)
Chikungunya Fever/epidemiology , Chikungunya Fever/virology , Adolescent , Chikungunya Fever/diagnosis , Chikungunya virus/classification , Chikungunya virus/genetics , Chikungunya virus/isolation & purification , Child , Child, Preschool , Cross-Sectional Studies , Female , Fever/diagnosis , Fever/epidemiology , Fever/virology , Genotype , Humans , Incidence , Infant , Kenya/epidemiology , Male , Phylogeny , Prevalence , Prospective Studies , Recurrence
15.
Viruses ; 14(1)2021 12 31.
Article in English | MEDLINE | ID: mdl-35062275

ABSTRACT

Chikungunya virus (CHIKV) is an alphavirus transmitted by Aedes mosquitoes, which causes Chikungunya fever. Three CHIKV genotypes have been identified: West African, East-Central-South African and Asian. In 2014, CHIKV was detected for the first time in Mexico, accumulating 13,569 confirmed cases in the following three years. Studies on the molecular diversification of CHIKV in Mexico focused on limited geographic regions or investigated only one structural gene of the virus. To describe the dynamics of this outbreak, we analyzed 309 serum samples from CHIKV acute clinical cases from 15 Mexican states. Partial NSP3, E1, and E2 genes were sequenced, mutations were identified, and their genetic variability was estimated. The evolutionary relationship with CHIKV sequences sampled globally were analyzed. Our sequences grouped with the Asian genotype within the Caribbean lineage, suggesting that the Asian was the only circulating genotype during the outbreak. Three non-synonymous mutations (E2 S248F and NSP3 A437T and L451F) were present in our sequences, which were also identified in sequences of the Caribbean lineage and in one Philippine sequence. Based on the phylogeographic analysis, the viral spread was reconstructed, suggesting that after the introduction through the Mexican southern border (Chiapas), CHIKV dispersed to neighboring states before reaching the center and north of the country through the Pacific Ocean states and Quintana Roo. This is the first viral phylogeographic reconstruction in Mexico characterizing the CHIKV outbreak across the country.


Subject(s)
Chikungunya Fever/virology , Chikungunya virus/classification , Chikungunya virus/genetics , Genetic Variation , Molecular Epidemiology , Aedes/virology , Animals , Caribbean Region , Chikungunya Fever/epidemiology , Disease Outbreaks , Genotype , Mexico/epidemiology , Mutation , Pacific Ocean , Phylogeny , Phylogeography
16.
Semin Cell Dev Biol ; 111: 148-155, 2021 03.
Article in English | MEDLINE | ID: mdl-32665176

ABSTRACT

Alphaviruses such as chikungunya and western equine encephalitis viruses are important human pathogens transmitted by mosquitoes that have recently caused large epidemic and epizootic outbreaks. The epidemic potential of alphaviruses is often related to enhanced mosquito transmission. Tissue barriers and antiviral responses impose bottlenecks to viral populations in mosquitoes. Substitutions in the envelope proteins and the presence of repeated sequence elements (RSEs) in the 3'UTR of epidemic viruses were proposed to be specifically associated to efficient replication in mosquito vectors. Here, we discuss the molecular mechanisms that originated RSEs, the evolutionary forces that shape the 3'UTR of alphaviruses, and the significance of RSEs for mosquito transmission. Finally, the presence of RSEs in the 3'UTR of viral genomes appears as evolutionary trait associated to mosquito adaptation and emerges as a common feature among viruses from the alphavirus and flavivirus genera.


Subject(s)
Alphavirus Infections/transmission , Chikungunya virus/genetics , Encephalitis Virus, Western Equine/genetics , Flavivirus Infections/transmission , Flavivirus/genetics , Genome, Viral , Viral Envelope Proteins/genetics , 3' Untranslated Regions , Alphavirus Infections/virology , Animals , Chikungunya virus/classification , Chikungunya virus/pathogenicity , Culicidae/virology , Encephalitis Virus, Western Equine/classification , Encephalitis Virus, Western Equine/pathogenicity , Flavivirus/classification , Flavivirus/pathogenicity , Flavivirus Infections/virology , Gene Expression Regulation , Humans , Microsatellite Repeats , Mosquito Vectors/virology , Phylogeny , Signal Transduction , Viral Envelope Proteins/metabolism , Virus Replication
17.
Viruses ; 12(11)2020 11 23.
Article in English | MEDLINE | ID: mdl-33238619

ABSTRACT

Vector competence refers to the ability of a vector to acquire, maintain, and transmit a pathogen. Collecting mosquito saliva in medium-filled capillary tubes has become the standard for approximating arbovirus transmission. However, this method is time-consuming and labor-intensive. Here we compare the capillary tube method to an alternative high-throughput detection method the collection of saliva on paper cards saturated with honey, with (FTA card) and without (filter paper) reagents for the preservation of nucleic acid for Aedes aegypti and Aedes albopictus mosquitoes infected with two emerging genotypes of the chikungunya virus (CHIKV). Model results showed that the Asian genotype CHIKV dissemination in the harvested legs of both Ae. aegypti and Ae. albopictus increased the odds of females having a positive salivary infection and higher salivary viral titers, while for the IOL genotype the same effect was observed only for Ae. aegypti. Of the three tested detection methods, the FTA card was significantly more effective at detecting infected saliva of Ae. aegypti and Ae. albopictus females than the capillary tube and filter paper was as effective as the capillary tube for the Asian genotype. We did not find significant effects of the detection method in detecting higher viral titer for both Asian and IOL genotypes. Our results are discussed in light of the limitations of the different tested detection methods.


Subject(s)
Aedes/virology , Arbovirus Infections/virology , Chikungunya virus/genetics , Saliva/virology , Viral Load/methods , Animals , Chikungunya virus/classification , Female , Genotype , Male , Mosquito Vectors/virology , Paper
18.
PLoS One ; 15(11): e0241754, 2020.
Article in English | MEDLINE | ID: mdl-33156857

ABSTRACT

Between late 2017 and mid-2018, a chikungunya fever outbreak occurred in Mombasa, Kenya that followed an earlier outbreak in mid-2016 in Mandera County on the border with Somalia. Using targeted Next Generation Sequencing, we obtained genomes from clinical samples collected during the 2017/2018 Mombasa outbreak. We compared data from the 2016 Mandera outbreak with the 2017/2018 Mombasa outbreak, and found that both had the Aedes aegypti adapting mutations, E1:K211E and E2:V264A. Further to the above two mutations, 11 of 15 CHIKV genomes from the Mombasa outbreak showed a novel triple mutation signature of E1:V80A, E1:T82I and E1:V84D. These novel mutations are estimated to have arisen in Mombasa by mid-2017 (2017.58, 95% HPD: 2017.23, 2017.84). The MRCA for the Mombasa outbreak genomes is estimated to have been present in early 2017 (2017.22, 95% HPD: 2016.68, 2017.63). Interestingly some of the earliest genomes from the Mombasa outbreak lacked the E1:V80A, E1:T82I and E1:V84D substitutions. Previous laboratory experiments have indicated that a substitution at position E1:80 in the CHIKV genome may lead to increased CHIKV transmissibility by Ae. albopictus. Genbank investigation of all available CHIKV genomes revealed that E1:V80A was not present; therefore, our data constitutes the first report of the E1:V80A mutation occurring in nature. To date, chikungunya outbreaks in the Northern and Western Hemispheres have occurred in Ae. aegypti inhabited tropical regions. Notwithstanding, it has been suggested that an Ae. albopictus adaptable ECSA or IOL strain could easily be introduced in these regions leading to a new wave of outbreaks. Our data on the recent Mombasa CHIKV outbreak has shown that a potential Ae. albopictus adapting mutation may be evolving within the East African region. It is even more worrisome that there exists potential for emergence of a CHIKV strain more adapted to efficient transmission by both Ae. albopictus and Ae.aegypti simultaneously. In view of the present data and history of chikungunya outbreaks, pandemic potential for such a strain is now a likely possibility in the future. Thus, continued surveillance of chikungunya backed by molecular epidemiologic capacity should be sustained to understand the evolving public health threat and inform prevention and control measures including the ongoing vaccine development efforts.


Subject(s)
Chikungunya Fever/diagnosis , Chikungunya virus/classification , High-Throughput Nucleotide Sequencing/standards , Mutation, Missense , Viral Proteins/genetics , Whole Genome Sequencing/methods , Aedes/virology , Amino Acid Substitution , Animals , Chikungunya Fever/virology , Chikungunya virus/genetics , Disease Outbreaks , Humans , Kenya , Mosquito Vectors/virology , Phylogeny , Sequence Analysis, RNA , Tropical Climate
19.
Viruses ; 12(11)2020 11 17.
Article in English | MEDLINE | ID: mdl-33213040

ABSTRACT

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 Aedes albopictus. 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.


Subject(s)
Chikungunya Fever/epidemiology , Chikungunya virus/classification , Chikungunya virus/genetics , Disease Outbreaks , Genotype , Phylogeny , Aedes/virology , Amino Acid Substitution , Animals , Bangladesh/epidemiology , Genome, Viral , Humans , Mosquito Vectors/virology , Thailand/epidemiology , Viral Envelope Proteins/genetics , Virus Replication
20.
J Infect Dis ; 222(Suppl 8): S709-S716, 2020 10 29.
Article in English | MEDLINE | ID: mdl-33119099

ABSTRACT

BACKGROUND: The role of human mobility in the epidemiology of emerging Aedes-transmitted viral diseases is recognized but not fully understood. The objective of this systematic review and meta-analysis was to examine how human mobility patterns are driving chikungunya outbreaks. METHODS: Literature was systematically reviewed for studies on chikungunya prevalence in countries/territories with high-level evidence of human mobility-driven outbreaks, based on: (1) emergence of chikungunya outbreaks with epidemic chikungunya virus genotypes among displaced/migrant populations and their hosting communities; and (2) identification of imported index case(s) with epidemic genotypes phylogenetically related to the genotypes circulating during emerging or subsequent outbreaks. RESULTS: The meta-analysis of extracted prevalence data revealed that a large proportion of the population in countries/territories afflicted by outbreaks is still at risk of infection during future outbreaks. On the other hand, approximately one-half of suspected chikungunya cases could be infected with other co-circulating acute febrile illnesses. CONCLUSIONS: We discussed in this paper how human mobility-driven chikungunya outbreaks can be addressed, and how the involvement of several sectors in addition to the health sector in multisectoral approaches (MSAs) is important for prevention and control of chikungunya and other Aedes-transmitted arboviral outbreaks.


Subject(s)
Chikungunya Fever/epidemiology , Communicable Disease Control/methods , Disease Outbreaks/prevention & control , Population Dynamics/trends , Chikungunya virus/classification , Chikungunya virus/genetics , Coinfection/epidemiology , Genotype , Humans , Intersectoral Collaboration , Phylogeny , Prevalence
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