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Pollett, S.

Publications and source records attributed to Pollett, S..

15 recordsLinked to original sources

Repeated SARS-CoV-2 Antigenic Exposures from Prior Vaccinations and Infections Demonstrate Limits of Antibody Durability and Breadth Against Newer Variants

BackgroundWidespread immunity from vaccination and infection has reduced COVID-19 morbidity and mortality, but this immunity varies across the population. Understanding how repeated antigenic exposures influence antibody responses helps to inform future vaccination strategies. MethodsSerum samples collected one and six months after XBB.1.5 vaccination from 25 generally healthy healthcare workers with varying exposure histories were assessed for neutralizing activity against a range of variants, from pre-Omicron variants to latest Omicron JN.1 sublineage variants and divergent BA.3.2 variants, using lentiviral pseudoviruses. Participants were stratified by vaccination and infection history. ResultsXBB.1.5 vaccination elicited broad neutralizing responses, with strong boosting against previously encountered antigens relative to vaccine-matched XBB.1.5 and newer variants. Geometric mean neutralization titers were generally comparable across exposure groups, indicating limited influence of prior Omicron infection or bivalent vaccination, though intra-group heterogeneity was observed. At six months, overall titers declined by 36-62%. Titers remained highest against the pre-Omicron and lowest against JN.1 sublineage variants. N-terminal glycosylation (DelS31, T22N) modestly affected neutralization. ConclusionsXBB.1.5 vaccination elicited broad neutralizing antibody responses against previously encountered and vaccine-matched antigens regardless of exposure history, but titers waned after six months. This waning, compounded by continued emergence of immune-evasive variants and heterogenous population immunity, underscores the need for continually monitoring neutralizing antibody durability and breadth to guide evidence-based COVID-19 vaccine formulation updates.

microbiology↗

Antigenic cartography using hamster sera identifies SARS-CoV-2 JN.1 evasion seen in human XBB.1.5 booster sera

Antigenic assessments of SARS-CoV-2 variants inform decisions to update COVID-19 vaccines. Primary infection sera are often used for assessments, but such sera are rare due to population immunity from SARS-CoV-2 infections and COVID-19 vaccinations. Here, we show that neutralization titers and breadth of matched human and hamster pre-Omicron variant primary infection sera correlate well and generate similar antigenic maps. The hamster antigenic map shows modest antigenic drift among XBB sub-lineage variants, with JN.1 and BA.4/BA.5 variants within the XBB cluster, but with five to six-fold antigenic differences between these variants and XBB.1.5. Compared to sera following only ancestral or bivalent COVID-19 vaccinations, or with post-vaccination infections, XBB.1.5 booster sera had the broadest neutralization against XBB sub-lineage variants, although a five-fold titer difference was still observed between JN.1 and XBB.1.5 variants. These findings suggest that antibody coverage of antigenically divergent JN.1 could be improved with a matched vaccine antigen.

microbiology↗

Comparative Analysis of SARS-CoV-2 Antigenicity across Assays and in Human and Animal Model Sera

The antigenic evolution of SARS-CoV-2 requires ongoing monitoring to judge the immune escape of newly arising variants. A surveillance system necessitates an understanding of differences in neutralization titers measured in different assays and using human and animal sera. We compared 18 datasets generated using human, hamster, and mouse sera, and six different neutralization assays. Titer magnitude was lowest in human, intermediate in hamster, and highest in mouse sera. Fold change, immunodominance patterns and antigenic maps were similar among sera. Most assays yielded similar results, except for differences in fold change in cytopathic effect assays. Not enough data was available for conclusively judging mouse sera, but hamster sera were a consistent surrogate for human first-infection sera.

bioinformatics↗

Comparative population genomics of manta rays has global implications for management

Understanding population connectivity and genetic diversity is of fundamental importance to conservation. However, in globally threatened marine megafauna, challenges remain due to their elusive nature and wide-ranging distributions. As overexploitation continues to threaten biodiversity across the globe, such knowledge gaps compromise both the suitability and effectiveness of management actions. Here, we use a comparative framework to investigate genetic differentiation and diversity of manta rays, one of the most iconic yet vulnerable groups of elasmobranchs on the planet. Despite their recent divergence, we show how oceanic manta rays (Mobula birostris) display significantly higher heterozygosity than reef manta rays (Mobula alfredi) and that M. birostris populations display higher connectivity worldwide. Through inferring modes of colonisation, we reveal how both contemporary and historical forces have likely influenced these patterns, with important implications for population management. Our findings highlight the potential for fisheries to disrupt population dynamics at both local and global scales and therefore have direct relevance for international conservation of marine species.

evolutionary biology↗

Post-vaccination Omicron infections induce broader immunity across antigenic space than prototype mRNA COVID-19 booster vaccination or primary infection

The rapid emergence of new SARS-CoV-2 variants challenges vaccination strategies. Here, we measured antigenic diversity among variants and interpreted neutralizing antibody responses following single and multiple exposures in longitudinal infection and vaccine cohorts. Antigenic cartography using primary infection antisera showed that BA.2, BA.4/BA.5, and BA.2.12.1 are distinct from BA.1 and closer to the Beta cluster. Three doses of an mRNA COVID-19 vaccine increased breadth to BA.1 more than to BA.4/BA.5 or BA.2.12.1. Omicron BA.1 post-vaccination infection elicited antibody landscapes characterized by broader immunity across antigenic space than three doses alone, although with less breadth than expected to BA.2.12.1 and BA.4/BA.5. Those with Omicron BA.1 infection after two or three vaccinations had similar neutralizing titer magnitude and antigenic breadth. Accounting for antigenic differences among variants of concern when interpreting neutralizing antibody titers aids understanding of complex patterns in humoral immunity and informs selection of future COVID-19 vaccine strains.

microbiology↗

A systematic review and meta-analysis of the potential non-human animal reservoirs and arthropod vectors of the Mayaro virus

Improving our understanding of Mayaro virus (MAYV) ecology is critical to guide surveillance and risk assessment. We conducted a PRISMA-adherent systematic review of the published and grey literature to identify potential arthropod vectors and non-human animal reservoirs of MAYV. We searched PubMed, Embase, Web of Science, SciELO and grey-literature sources including PAHO databases and dissertation repositories. Studies were included if they assessed MAYV virological/immunological measured occurrence in field-caught, domestic, or sentinel animals or in field-caught arthropods. We conducted an animal seroprevalence meta-analysis using a random effects model. We compiled granular georeferenced maps of non-human MAYV occurrence and graded the quality of the studies using a customized framework. Overall, 57 studies were eligible out of 1523 screened, published between the years 1961 and 2020. Seventeen studies reported MAYV positivity in wild mammals, birds, or reptiles and five studies reported MAYV positivity in domestic animals. MAYV positivity was reported in 12 orders of wild-caught vertebrates, most frequently in the orders Charadriiformes and Primate. Sixteen studies detected MAYV in wild-caught mosquito genera including Haemagogus, Aedes, Culex, Psorophora, Coquillettidia, and Sabethes. Vertebrate animals or arthropods with MAYV were detected in Brazil, Panama, Peru, French Guiana, Colombia, Trinidad, Venezuela, Argentina, and Paraguay. Among non-human vertebrates, the Primate order had the highest pooled prevalence (PP) at 13.1% (95% CI: 4.3-25.1%). From the three most studied primate genera we found the highest prevalence was in Alouatta (PP: 32.2%, 95% CI: 0.0-79.2%), followed by Callithrix (PP: 17.8%, 95% CI: 8.6-28.5%), and Cebus/Sapajus (PP: 3.7%, 95% CI: 0.0-11.1%). We further found that MAYV occurs in a wide range of vectors beyond Haemagogus spp. The quality of evidence behind these findings was variable and prompts calls for standardization of reporting of arbovirus occurrence. These findings support further risk emergence prediction, guide field surveillance efforts, and prompt further in-vivo studies to better define the ecological drivers of MAYV maintenance and potential for emergence. Author SummaryMayaro virus (MAYV) is an emerging tropical public health threat in the Americas. We conducted a georeferenced, quality-graded systematic review to evaluate the current evidence regarding MAYV occurrence in non-human vertebrates and arthropods. Overall, 57 studies were eligible out of 1523 screened, published between the years 1961 and 2020. Seventeen studies reported MAYV positivity in wild mammals, birds, or reptiles and five studies reported MAYV positivity in domestic animals. MAYV positivity was reported in 12 orders of wild-caught vertebrates, most frequently in the orders Charadriiformes and Primate. Our systematic review identified 12 orders of wild-caught vertebrates and seven mosquito genera with evidence of MAYV occurrence. Primates had the highest pooled MAYV prevalence according to a seroprevalence meta-analysis. The graded quality of evidence behind these findings was variable and prompts calls for standardization of reporting of MAYV and perhaps other emerging arbovirus occurrence in animals and vectors. This study provides important information for public health authorities and disease ecologists concerned with the growing threat of MAYV in Latin America. Our analysis provides a foundation for future laboratory and field studies focused on the MAYV transmission cycle.

ecology↗

High confidence identification of intra-host single nucleotide variants for person-to-person influenza transmission tracking in congregate settings

Influenza within-host viral populations are the source of all global influenza diversity and play an important role in driving the evolution and escape of the influenza virus from human immune responses, antiviral treatment, and vaccines, and have been used in precision tracking of influenza transmission chains. Next Generation Sequencing (NGS) has greatly improved our ability to study these populations, however, major challenges remain, such as accurate identification of intra-host single nucleotide variants (iSNVs) that represent within-host viral diversity of influenza virus. In order to investigate the sources and the frequency of called iSNVs in influenza samples, we used a set of longitudinal influenza patient samples collected within a University of Maryland (UMD) cohort of college students in a living learning community. Our results indicate that technical replicates aid in removal of random RT-PCR, PCR, and platform sequencing errors, while the use of clonal plasmids for removal of systematic errors is more important in samples of low RNA abundance. We show that the choice of reference for read mapping affects the frequency of called iSNVs, with the sample self-reference resulting in the lowest amount of iSNV noise. The importance of variant caller choice is also highlighted in our study, as we observe differential sensitivity of variant callers to the mapping reference choice, as well as the poor overlap of their called iSNVs. Based on this, we develop an approach for identification of highly probable iSNVs by removal of sequencing and bioinformatics algorithm-associated errors, which we implement in phylogenetic analyses of the UMD samples for a greater resolution of transmission links. In addition to identifying closely related transmission connections supported by the presence of highly confident shared iSNVs between patients, our results also indicate that the rate of minor variant turnover within a host may be a limiting factor for utilization of iSNVs to determine patient epidemiological links.

genomics↗

An ecological niche model to predict the geographic distribution of Haemagogus janthinomys, Dyar, 1921 the yellow fever and Mayaro virus vector, in South America

Yellow fever virus (YFV) has a long history of impacting human health in South America. Mayaro virus (MAYV) is an emerging arbovirus of public health concern in the Neotropics and its full impact is yet unknown. Both YFV and MAYV are primarily maintained via a sylvatic transmission cycle but can be opportunistically transmitted to humans by the bites of infected forest dwelling Haemagogus janthinomys Dyar, 1921. To better understand the potential risk of YFV and MAYV transmission to humans, a more detailed understanding of this vector species distribution is critical. This study compiled a comprehensive database of 170 unique Hg. janthinomys collection sites retrieved from the published literature, digitized museum specimens and publicly accessible mosquito surveillance data. Covariate analysis was performed to optimize a selection of environmental (topographic and bioclimatic) variables associated with predicting habitat suitability, and species distributions modelled across South America using a maximum entropy (MaxEnt) approach. Our results indicate that suitable habitat for Hg. janthinomys can be found across forested regions of South America including the Atlantic forests and interior Amazon. Author SummaryMayaro virus is a neglected tropical disease and there is insufficient evidence to define its geographic range. The mosquito Haemagogus janthinomys is a primary vector of Mayaro and its distribution is largely unknown at a sub-country scale. Building compendiums of collection data and creating ecological niche models provides a more precise estimation vector species potential habitat. Our dataset stands as one of the most expansive existing for collection data of this species combining data published in literature, publicly available data repositories and digitized museum specimen records. Comparing results of niche models with near real time environmental data can give even better predictions of areas where Mayaro virus exposure could occur. The methods and results of this study can be replicated for any disease/vector of interest so long as there is data discoverable through the scientific literature, public repositories, or other civilian and governmental agencies willing to share.

ecology↗

A comparative recombination analysis of human coronaviruses and implications for the SARS-CoV-2 pandemic

The SARS-CoV-2 pandemic prompts evaluation of recombination in human coronavirus (hCoV) evolution. We undertook recombination analyses of 158,118 public seasonal hCoV, SARS-CoV-1, SARS-CoV-2 and MERS-CoV genome sequences using the RDP4 software. We found moderate evidence for 8 SARS-CoV-2 recombination events, two of which involved the spike gene, and low evidence for one SARS-CoV-1 recombination event. Within MERS-CoV, 229E, OC43, NL63 and HKU1 datasets, we noted 7, 1, 9, 14, and 1 high-confidence recombination events, respectively. There was propensity for recombination breakpoints in structural genes, and recombination severely skewed the temporal structure of these data, especially for NL63 and OC43. Bayesian time-scaled analyses on recombinant-free data indicated the sampled diversity of seasonal CoVs emerged in the last 70 years, with 229E displaying continuous lineage replacements. These findings emphasize the importance of genomic based surveillance to detect recombination in SARS-CoV-2, particularly if recombination may lead to immune evasion.

genomics↗

Inoculation by mosquito induces durable differences in serological profile in non-human primates infected with DENV1

Natural dengue virus (DENV) infections are delivered by mosquito bite but how the route of inoculation route could shape the humoral immune response is not well understood. Here, we serologically profiled 20 non-human primates (NHP) from a prior study of DENV1 infection in which the animals were inoculated by mosquito (N=10) or subcutaneous injection (N=10). Using a comprehensive, densely tiled and highly redundant pan-flavivirus programmable phage library containing 91,562 overlapping 62 amino acid peptides, we produced a high-resolution map of linear peptide sequences enriched during DENV seroconversion. We found that serological profiles in mosquito-inoculated and subcutaneously-inoculated animals were similar up to 90 days after primary infection, but diverged at 1 year. We found differences in sero-reactivity, as indicated by the median area under the curve (AUC) in the Envelope (E; residues 215-406; p < 0.08), and Nonstructural-3 (NS3; residues 549-615; p < 0.05) proteins in mosquito-inoculated versus subcutaneously-inoculated animals. Within the E protein, residues 339-384 in domain III accounted for >99% of the total AUC difference across residues 215-406. Antibody breadth did not vary by mode of inoculation. The differential reactivity to E domain III (EDIII) seen by phage display validated orthogonally by ELISA, but did not correlate with late neutralization titers. Serological profiling of humoral immune responses to DENV infection in NHP by programmable phage display demonstrated durable differences in sero-reactivity by route of inoculation. These findings could have implications for DENV diagnostics and evaluation of vaccines. IMPORTANCEDengue virus (DENV) infections are transmitted by mosquito bite, but how being infected by mosquito bite affects the immune response is not known. In this study, we analyzed antibodies produced by rhesus macaques infected with DENV using programmable phage display, a high-throughput method for characterizing what viral protein derived peptides serum antibodies bind to. We found that while there was no difference in antibody binding profiles at early timepoints post-infection, at one year post-infection, there were substantial differences in the antibody binding profiles of macaques who were infected by mosquito bite versus those that were infected by injection. In general, antibodies in the macaques inoculated by mosquito maintained higher levels of sero-reactivity, with a strong signal still present one year post-infection. The findings we report could have implications for DENV diagnostics and evaluation of DENV vaccines.

immunology↗

Vector and cell-culture passaging of dengue clinical samples for virus isolation and amplification does not significantly change genome consensus or frequencies of intra-host viral variants

Intra-host single nucleotide variants (iSNVs) have been increasingly used in genomic epidemiology to increase phylogenetic resolution and reconstruct fine-scale outbreak dynamics. These analyses are preferably done on sequence data from direct clinical samples, but in many cases due to low viral loads, there might not be enough genetic material for deep sequencing and iSNV determination. Isolation of the virus from clinical samples with low passage number increases viral load, but to date, no studies have investigated how dengue virus (DENV) culture isolation from a clinical sample impacts the consensus sequence, and there is no information on the intra-host virus population changes that may result from viral isolation. In this study, we investigate consensus and iSNV frequency differences between DENV sequenced directly from clinical samples and their corresponding low-passage isolates. Twenty five DENV1 and DENV2 positive sera and their corresponding viral isolates (T.splendens inoculation and C6/36 passage) were obtained from a prospective cohort study in the Philippines. These were sequenced on MiSeq with minimum nucleotide depth of coverage of 1000x, and iSNVs were detected using LoFreq. For both DENV1 and DENV2, we found that the nucleotide call concordance (including called iSNVs with variant cutoff at 5%) between direct sera sample and its cultured virus was on average 99.99%. There were a maximum of one consensus nucleotide difference between clinical sample and isolate. Interestingly, we found that iSNV frequencies were also largely preserved between the samples, with an average difference in minor variant frequency of 6.8% (95CI: 3.6%-10%) and 9.6% (95CI: 7%-12.2%) for DENV1 and DENV2, respectively. Furthermore, we found no significant differences in either DENV1 or DENV2 between the sample pairs (clinical sample and isolate) in their number of iSNV positions per genome, or in the difference in variant frequencies (p=0.36 and p=0.13, respectively, F-test). Our results show that low-passage DENV isolates may be used for identification of the majority of their human-derived within-host variant populations, which are increasingly being used for precision tracking of DENV and other RNA viruses.

evolutionary biology↗

The evolution of dengue-2 viruses in Malindi, Kenya and greater East Africa: epidemiological and immunological implications

Kenya experiences a substantial burden of dengue, yet there are very few DENV-2 sequence data available from this country and indeed the entire continent of Africa. We therefore undertook whole genome sequencing and evolutionary analysis of fourteen dengue virus (DENV)-2 strains sampled from Malindi sub-County Hospital during the 2017 DENV-2 outbreak in the Kenyan coast. We further performed an extended East African phylogenetic analysis, which leveraged 26 complete African env genes. Maximum likelihood analysis showed that the 2017 outbreak was due to the Cosmopolitan genotype, indicating that this has been the only confirmed human DENV-2 genotype circulating in Africa to date. Phylogeographic analyses indicated transmission of DENV-2 viruses between East Africa and South/South-West Asia. Time-scaled genealogies show that DENV-2 viruses are spatially structured within Kenya, with a time-to-most-common-recent ancestor analysis indicating that these DENV-2 strains were circulating for up to 5.38 years in Kenya before detection in the 2017 Malindi outbreak. Selection pressure analyses indicated sampled Kenyan DENV strains uniquely being under positive selection at 6 sites, predominantly across the non-structural genes, and epitope prediction analyses showed that one of these sites corresponds to a putative predicted MHC-I CD8+ DENV-2 Cosmopolitan virus epitope only evident in a sampled Kenyan virus. Taken together, our findings indicate that the 2017 Malindi DENV-2 outbreak arose from a strain which had circulated for several years in Kenya before recent detection, has experienced diversifying selection pressure, and may contain new putative immunogens relevant to vaccine design. These findings prompt further genomic epidemiology studies in this and other Kenyan locations to further elucidate the transmission dynamics of DENV in this region. Author summary (non-technical)Kenya experiences a substantial burden of dengue, yet the patterns of dengue spread in this region are unclear. Evolutionary analyses of dengue virus strain sequences could offer major insights into the spread of dengue viruses in this region, but there are very few DENV-2 sequence data available from this country and indeed the entire continent of Africa. We therefore undertook whole genome sequencing and evolutionary analysis of fourteen dengue virus (DENV)-2 strains sampled from Malindi sub-County Hospital during the 2017 DENV-2 outbreak in the Kenyan coast. We further performed an extended East African phylogenetic analysis, which leveraged 26 complete African env genes. Our results indicated transmission of DENV-2 viruses between East Africa and South/South-West Asia, that there is localized spread of DENV-2 viruses within Kenya, and that Kenyan DENV-2 strains were circulating for up to 5.38 years in Kenya before detection in the 2017 Coastal outbreak. We further performed selection pressure analyses and identified possible new markers of DENV-2 immune recognition specific to this population, with relevance to vaccine design.

genomics↗

A systematic review and evaluation of Zika virus forecasting and prediction research during a public health emergency of international concern

INTRODUCTIONEpidemic forecasting and prediction tools have the potential to provide actionable information in the midst of emerging epidemics. While numerous predictive studies were published during the 2016-2017 Zika Virus (ZIKV) pandemic, it remains unknown how timely, reproducible and actionable the information produced by these studies was.\n\nMETHODSTo improve the functional use of mathematical modeling in support of future infectious disease outbreaks, we conducted a systematic review of all ZIKV prediction studies published during the recent ZIKV pandemic using the PRISMA guidelines. Using MEDLINE, EMBASE and grey literature review, we identified studies that forecasted, predicted or simulated ecological or epidemiological phenomenon related to the Zika pandemic that were published as of March 01, 2017. Eligible studies underwent evaluation of objectives, data sources, methods, timeliness, reproducibility, accessibility and clarity by independent reviewers.\n\nRESULTS2034 studies were identified, of which n = 73 met eligibility criteria. Spatial spread, R0 (basic reproductive number) and epidemic dynamics were most commonly predicted, with few studies predicting Guillain-Barre Syndrome burden (4%), sexual transmission risk (4%) and intervention impact (4%). Most studies specifically examined populations in the Americas (52%), with few African-specific studies (4%). Case count (67%), vector (41%) and demographic data (37%) were the most common data sources. Real-time internet data and pathogen genomic information were used in 7% and 0% of studies, respectively, and social science and behavioral data were typically absent in modeling efforts. Deterministic models were favored over stochastic approaches. Forty percent of studies made model data entirely available, 29% provided all relevant model code, 43% presented uncertainty in all predictions and 54% provided sufficient methodological detail allowing complete reproducibility. Fifty-one percent of predictions were published after the epidemic peak in the Americas. While the use of preprints improved the accessibility of ZIKV predictions by a median 119 days sooner than journal publication dates, they were used in only 30% of studies.\n\nCONCLUSIONSMany ZIKV predictions were published during the 2016-2017 pandemic. The accessibility, reproducibility, timeliness, and incorporation of uncertainty in these published predictions varied and indicates that there is substantial room for improvement. To enhance the utility of analytical tools for outbreak response, it is essential to improve the sharing of model data, code, and preprints for future outbreaks, epidemics and pandemics.\n\nAuthor summaryResearchers published many studies which sought to predict and forecast important features of Zika virus (ZIKV) infections and their spread during the 2016-2017 ZIKV pandemic. We conducted a comprehensive review of such ZIKV prediction studies and evaluated their aims, the data sources they used, which methods were used, how timely they were published, and whether they provided sufficient information to be used or reproduced by others. Of the 73 studies evaluated, we found that the accessibility, reproducibility, timeliness, and incorporation of uncertainty in these published predictions varied and indicates that there is substantial room for improvement. We identified that the release of study findings before formal journal publication ( pre-prints) increased the timeliness of Zika prediction studies, but note they were infrequently used during this public health emergency. Addressing these areas can improve our understanding of Zika and other outbreaks and ensure that forecasts can inform preparedness and response to future outbreaks, epidemics and pandemics.

epidemiology↗

Phylogenomics and species delimitation of mobulid rays reveals cryptic diversity and a new species of manta ray

Practical biodiversity conservation relies on delineation of biologically meaningful units, particularly with respect to global conventions and regulatory frameworks. Traditional approaches have typically relied on morphological observation, resulting in artificially broad delineations and non-optimal species units for conservation. More recently, species delimitation methods have been revolutionised with High-Throughput Sequencing approaches, allowing study of diversity within species radiations using genome-wide data. The highly mobile elasmobranchs, manta and devil rays (Mobula spp.), are threatened globally by targeted and bycatch fishing pressures resulting in recent protection under several global conventions. However, a lack of global data, morphological similarities, a succession of recent taxonomic changes and ineffectual traceability measures combine to impede development and implementation of a coherent and enforceable conservation strategy. Here, we generate genome-wide Single Nucleotide Polymorphism (SNP) data from among the most globally and taxonomically representative set of mobulid tissues. The resulting phylogeny and delimitation of species units represents the most comprehensive assessment of mobulid diversity with molecular data to date. We find a mismatch between current species classifications, and optimal species units for effective conservation. Specifically, we find robust evidence for an undescribed species of manta ray in the Gulf of Mexico and show that species recently synonymised are reproductively isolated. Further resolution is achieved at the population level, where cryptic diversity is detected in geographically distinct populations, and indicates potential for future traceability work determining regional location of catch. We estimate the optimal species tree and uncover substantial incomplete lineage sorting, where standing variation in extinct ancestral populations is identified as a driver of phylogenetic uncertainty, with further conservation implications. Our study provides a framework for molecular genetic species delimitation that is relevant to wide-ranging taxa of conservation concern, and highlights the potential for genomic data to support effective management, conservation and law enforcement strategies.

genomics↗

Recent outbreaks of chikungunya virus (CHIKV) in Africa and Asia are driven by a variant carrying mutations associated with increased fitness for Aedes aegypti

BackgroundIn 2016, a chikungunya virus (CHIKV) outbreak was reported in Mandera, Kenya. This was the first major CHIKV outbreak in the country since the global re-emergence of this virus, which arose as an initial outbreak in Kenya in 2004. Therefore, we collected samples and sequenced viral genomes from the 2016 Mandera outbreak.\n\nMethodology/Principal FindingsAll Kenyan genomes contained two mutations, E1:K211E and E2:V264A, recently reported to have an association with increased infectivity, dissemination and transmission in the Aedes aegypti (Ae. aegypti) vector. Phylogeographic inference of temporal and spatial virus relationships using Bayesian approaches showed that this Ae. aegypti adapted strain emerged within the East, Central, and South African (ECSA) lineage of CHIKV between 2005 and 2008, most probably in India. It was also in India where the first large outbreak caused by this strain appeared, in New Delhi, 2010. More importantly, our results also showed that this strain is no longer contained to India, and that it has more recently caused several major outbreaks of CHIKV, including the 2016 outbreaks in India, Pakistan and Kenya, and the 2017 outbreak in Bangladesh. In addition to its capability to cause large outbreaks in different regions of the world, this CHIKV strain has the capacity to replace less adapted wild type strains in Ae. aegypti-rich regions. Indeed, all the latest full CHIKV genomes of the ECSA Indian Ocean Lineage (IOL), from the regions of high Ae. aegypti prevalence, carry these two mutations, including samples collected in Japan, Australia, and China.\n\nConclusions/SignificanceOur results point to the importance of continued genomic-based surveillance of this strains global spread, and they prompt urgent vector competence studies in Asian and African countries, in order to assess the level of vector receptiveness, virus transmission, and the impact this might have on this strains ability to cause major outbreaks.\n\nAuthor summaryChikungunya virus (CHIKV) causes a debilitating infection with high fever, intense muscle and bone pain, rash, nausea, vomiting and headaches, and persistent and/or recurrent joint pains for months or years after contracting the virus. CHIKV is spread by two mosquito vectors, Aedes albopictus and Aedes aegypti, with increased presence around the globe. In this study, we report global spread of a CHIKV strain that carries two mutations that have been suggested to increase this virus ability to infect the Aedes aegypti mosquito, as well as to increase CHIKVs ability to be transmitted by this vector. We show that this strain appeared sometime between 2005 and 2008, most probably in India, and has now spread to Africa, Asia, and Australia. We show that this strain is capable of driving large outbreaks of CHIKV in the human population, causing recent major outbreaks in Kenya, Pakistan, India and Bangladesh. Thus, our results stress the importance of monitoring this strains global spread, as well as the need of improved vector control strategies in the areas of Aedes aegypti prevalence.

evolutionary biology↗