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Infections because of chikungunya and other mosquito-borne viruses, such as dengue and Zika, represent an area of significant unmet medical need. There are currently no approved medicines for prophylaxis or treatment of these diseases, and the development and implementation of vaccines against these viruses have proved problematic. Although antiviral molecules with treatment and prophylactic potential against the chikungunya virus have been identified, no successful field trials have been reported. Chemoprophylaxis may be attractive for unvaccinated at-risk populations; however, performing a successful chemoprophylaxis trial during a chikungunya outbreak will require a clearly identifiable at-risk population. We propose the application of a household transmission model as used in testing drugs against respiratory viruses. Current evidence on household clustering of chikungunya and other Aedes mosquito-borne viral infections is supportive. We suggest that this model may improve prophylaxis trial feasibility and focus research and future treatment on a population likely to benefit.

Acute febrile illness is a common presentation for patients at hospitals globally. Assays that can diagnose a variety of common pathogens in blood could help to establish a diagnosis for targeted disease management. We aimed to evaluate the performance of the BioFire Global Fever Panel (GF Panel), a multiplex nucleic acid amplification test performed on whole blood specimens run on the BioFire FilmArray System, in the diagnosis of several pathogens that cause acute febrile illness.We did a prospective, multicentre, cross-sectional diagnostic accuracy study to evaluate the GF Panel. Consenting adults and children older than 6 months presenting with fever in the previous 2 days were enrolled consecutively in sub-Saharan Africa (Ghana, Kenya, Tanzania, Uganda), southeast Asia (Cambodia, Thailand), central and South America (Honduras, Peru), and the USA (Washington, DC; St Louis, MO). We assessed the performance of six analytes (chikungunya virus, dengue virus [serotypes 1-4], Leptospira spp, Plasmodium spp, Plasmodium falciparum, and Plasmodium vivax or Plasmodium ovale) on the GF Panel. The performance of the GF Panel was assessed using comparator PCR assays with different primers followed by bidirectional sequencing on nucleic acid extracts from the same specimen. We calculated the positive percent agreement and negative percent agreement of the GF Panel with respect to the comparator assays. This study is registered with ClinicalTrials.gov, NCT02968355.From March 26, 2018, to Sept 30, 2019, 1965 participants were enrolled at ten sites worldwide. Of the 1875 participants with analysable results, 980 (52·3%) were female and the median age was 22 years (range 0-100). At least one analyte was detected in 657 (35·0%) of 1875 specimens. The GF Panel had a positive percent agreement for the six analytes evaluated as follows: chikungunya virus 100% (95% CI 86·3-100), dengue virus 94·0% (90·6-96·5), Leptospira spp 93·8% (69·8-99·8), Plasmodium spp 98·3% (96·3-99·4), P falciparum 92·7% (88·8-95·6), and P vivax or P ovale 92·7% (86·7-96·6). The GF Panel had a negative percent agreement equal to or greater than 99·2% (98·6-99·6) for all analytes.This 1 h sample-to-answer, molecular device can detect common causative agents of acute febrile illness with excellent positive percent agreement and negative percent agreement directly in whole blood. The targets of the assay are prevalent in tropical and subtropical regions globally, and the assay could help to provide both public health surveillance and individual diagnoses.BioFire Defense, Joint Project Manager for Medical Countermeasure Systems and US Army Medical Materiel Development Activity, and National Institute of Allergy and Infectious Diseases.

Mosquito-borne diseases such as dengue, chikungunya, and malaria have long been a health and economic burden in our society. Such illnesses develop after the pathogen, here arboviruses, are transmitted to humans by female mosquitoes during blood meals. In the case of dengue and chikungunya, such pathogens are transmitted to humans by infected

Chikungunya virus (CHIKV) is a major public health concern worldwide. However, infection levels are rarely known, especially in Africa. We recruited individuals from Ouagadougou, Burkina Faso and Lambaréné, Gabon (age range, 1–55 years), tested their blood for CHIKV antibodies, and used serocatalytic models to reconstruct epidemiological histories. In Ouagadougou, 291 of 999 (29.1%) individuals were seropositive, ranging from 2% among those aged

Post-chikungunya joint pain (arthritis or arthralgia) is a clinical concern in endemic regions as it may cause a debilitating illness sometimes years after the acute infection. This systematic review analyses evidence from controlled clinical trials regarding the efficacy of pharmacological and non-pharmacological interventions to treat post-chikungunya joint pain. PubMed, EMBASE, Scopus, Cochrane library and Web of Science were searched for eligible studies without any language or time limits, excluding retrospective studies, and prospective observational studies without a control group. Eleven studies met the inclusion criteria. Seven assessed pharmacological interventions and four assessed non-pharmacological interventions (exercise, neuromodulation). The number of participants in each intervention arm varied from 10 to 75 and, given the heterogeneity of interventions, a meta-analysis was not possible. Available evidence does not show any added benefit of chloroquine, hydroxychloroquine, stand-alone methotrexate or ribavirin compared with anti-inflammatory drugs or placebo/no treatment. Non-steroidal anti-inflammatory drugs may reduce pain up to 24 wk of treatment but long-term residual impact after stopping treatment is unassessed. Currently, there is also no high certainty evidence to recommend non-pharmacological methods such as exercise and neuromodulation.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus belonging to the Togaviridae family. The symptomatic infection is characterised by acute febrile disease which generally results in severe arthralgia and myalgia, however, most of the CHIKV infections remain asymptomatic. CHIKV RNA detection in asymptomatic volunteers may be responsible for the transfusion transmission of this infection, especially during outbreaks. There is no information for CHIKV seroprevalence among blood donors from the Federal District of Brazil.In early 2019, the Federal District of Brazil experienced a CHIKV outbreak, and this study evaluates the anti-CHIKV IgM and IgG presence in a well characterised cohort of blood donors from this region.Blood samples were collected from 450 volunteer blood donors during a CHIKV outbreak and tested for the presence of anti-CHIKV IgG and IgM antibodies using ELISA.The CHIKV seroprevalence was 0.89% (n = 4/450) and anti-CHIKV IgM prevalence was 1.11% (n = 5/450).The obtained results demonstrated that at least some of the blood donors have experienced CHIKV infection which can be related to a hypothetical risk of CHIKV transfusion transmission. More studies are necessary in order to examine the impact of CHIKV on blood transfusion.

Chikungunya is an important mosquito-borne disease caused by the arthritogenic chikungunya virus, characterized by sporadic outbreaks all around the world. Although CD4+ T cells seem to have an important role in the pathogenesis of chikungunya, the mechanisms involved in this process are not yet fully elucidated. The ectoenzymes CD39 and CD73, also expressed by CD4 T lymphocytes, are involved in the hydrolysis of pro-inflammatory extracellular ATP and generation of immunosuppressive adenosine and seem to be modulated in some arthritogenic pathologies. However, their involvement in Chikungunya disease is unclear. Thus, using flow cytometry, we investigated peripheral CD4+ T cells from patients with acute and chronic chikungunya to assess the expression of ectonucleotidases CD39 and CD73 and coinhibitory receptors and production of cytokine and cytolytic granules. Patients in the acute phase displayed increased levels of PD-1, CTLA-4, IL-10, and IFN-γ compared to healthy individuals and patients in the chronic phase. Moreover, during chronic Chikungunya, analyses of Mean Fluorescent Intensity (MFI) demonstrated a reduced density of LAP, Perforin and Granzyme B compared to the healthy control. Finally, reduced levels of the ectoenzymes CD39 and CD73 expression was found during the chronic phase suggesting a possible modulation of extracellular ATP and adenosine by CD4+ T cells that may be involved in the persistence of arthritogenic symptoms.

We sequenced a portion of the E1 envelope protein gene of two of four CHIKV RT-PCR-positive samples from the first cluster of chikungunya patients during the 2020 Chad outbreak. Phylogenetic analysis revealed that the viruses belonged to the East/Central/South/African genotype but lacked the E1 A226V and K211E mutations associated with viral adaptability and transmission, suggesting an autochthonous transmission. These sequences are a useful basis for tracking viral evolution in subsequent outbreaks in Chad.

In low-resource settings, resilience to infectious disease outbreaks can be hindered by limited access to diagnostic tests. Here we report the results of double-blinded studies of the performance of paper-based diagnostic tests for the Zika and chikungunya viruses in a field setting in Latin America. The tests involved a cell-free expression system relying on isothermal amplification and toehold-switch reactions, a purpose-built portable reader and onboard software for computer vision-enabled image analysis. In patients suspected of infection, the accuracies and sensitivities of the tests for the Zika and chikungunya viruses were, respectively, 98.5% (95% confidence interval, 96.2-99.6%, 268 serum samples) and 98.5% (95% confidence interval, 91.7-100%, 65 serum samples) and approximately 2 aM and 5 fM (both concentrations are within clinically relevant ranges). The analytical specificities and sensitivities of the tests for cultured samples of the viruses were equivalent to those of the real-time quantitative PCR. Cell-free synthetic biology tools and companion hardware can provide de-centralized, high-capacity and low-cost diagnostics for use in low-resource settings. Double-blinded studies show that paper-based diagnostic tests and a companion portable device designed for use in low-resource settings perform well for the diagnosis of the Zika and chikungunya viruses in serum samples.

In this paper, a nonlinear fractional-order chikungunya disease model that incorporates asymptomatic infectious individuals is proposed and analyzed. The main interest of this work is to investigate the role of memory effects on the dynamics of chikungunya. Qualitative analysis of the model’s equilibria showed that there exists a threshold quantity which governs persistence and extinction of the disease. Model parameters were estimated based on the 2015 weekly reported cases in Colombia. The Adams-Bashforth-Moulton method was used to numerically solve the proposed model. We investigated the role of asymptomatic infectious patients on short- and long-term dynamics of the diseases. We also determined threshold levels for the efficacy of preventative strategies that results in effective management of the disease. We believe that our model can provide invaluable insights for public health authorities to predict the effect of chikungunya transmission and analyze its underlying factors and to guide new control efforts.

Abstract: Chikungunya virus (CHIKV) is an Alphavirus (Togaviridae) responsible for Chikungunya fever (CHIKF) that is mainly characterized by a severe polyarthralgia, in which it is transmitted by the bite of infected Aedes aegypti and Ae. albopictus mosquitoes. Nowadays, there are no licensed vaccines or approved drugs to specifically treat this viral disease. Structural viral proteins participate in key steps of its replication cycle, such as viral entry, membrane fusion, nucleocapsid assembly, and virus budding. In this context, envelope E3-E2-E1 glycoproteins complex could be targeted for designing new drug candidates. In this review, aspects of the CHIKV entry mechanism are discussed to provide insights into assisting the drug discovery process. Moreover, several naturals, naturebased and synthetic compounds, as well as repurposed drugs and virtual screening are also explored as alternatives for developing CHIKV entry inhibitors. Finally, we provided a complementary analysis of studies involving inhibitors that were not explored by in silico methods. Based on this, Phe118, Val179, and Lys181 were found to be the most frequent residues, being present in 89.6, 82.7, and 93.1% of complexes, respectively. Lastly, some chemical aspects associated with interactions of these inhibitors and mature envelope E3- E2-E1 glycoproteins’ complex were discussed to provide data for scientists worldwide, supporting their search for new inhibitors against this emerging arbovirus.

Background We used surveillance data from Brazil and Colombia during 2007–2017 to assess the presence of socioeconomic inequalities on dengue, chikungunya and Zika at the neighborhood level in two Latin American cities. Methods To quantify the inequality, we estimated and decomposed the relative concentration index of inequality (RCI) accounting for the spatiotemporal distribution of the diseases. Results There were 281 426 arboviral cases notified in Fortaleza, Brazil, and 40 889 in Medellin, Colombia. The RCI indicated greater concentration of dengue cases among people living in low socioeconomic settings in both sites. The RCIs for chikungunya in Fortaleza covered the line of equality during their introduction in 2014, while the RCIs for Zika and chikungunya in Medellin indicated the presence of a small inequality. The RCI decomposition showed that year of notification and age were the main contributors to this inequality. In Medellin, the RCI decomposition showed that age and access to waste management accounted for 75.5%, 72.2% and 54.5% of the overall inequality towards the poor for dengue, chikungunya and Zika, respectively. Conclusions Our study presents estimates of the socioeconomic inequality of arboviruses and its decomposition in two Latin American cities. We corroborate the concentration of arboviral diseases in low socioeconomic neighborhoods and identify that year of occurrence, age, presence of healthcare facilities and waste management are key determinants of the heterogenous distribution of endemic arboviruses across the socioeconomic spectrum.

Phylogenetic analysis carried out in several Brazilian regions shows the circulation of the Asian and East-Central South African (ECSA) Chikungunya virus (CHIKV) genotypes in the country. Until now, there are no genetic studies about CHIKV strains circulating in the South region. In this study, we sequenced 5 new partial sequences of the CHIKV Envelope 1 gene from strains detected in Paraná state during the years 2016–2017. Maximum likelihood and neighbor-joining trees grouped all sequences in Brazilian branches within ECSA genotype and comparative analysis did not show E1-A226V mutation. However, we identified E1-K211T amino acid substitution in a sample demonstrating the dispersion of mutant strains in the country. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42770-022-00680-x.

Dengue virus (DENV), chikungunya virus (CHIKV), and Zika virus (ZIKV) are arboviruses that can affect maternal and fetal outcome if acquired during pregnancy. This study was done to estimate the positivity of DENV, CHIKV, and ZIKV in febrile pregnant women attending a tertiary care hospital in north India. Symptomatic pregnant women were tested for these viruses by IgM ELISA and/or by Trioplex real-time polymerase chain reaction. Their symptoms and laboratory parameters were recorded and were followed up till delivery to know their immediate delivery outcome. Of 104 women tested, 50 (48.1%) were positive for viral markers. Of these, evidence of infection by DENV, CHIKV, and both was found in 34 (32.7%), 10 (9.6%), and 6 (5.8%), respectively. ZIKV was not detected in any woman. Maximum DENV positivity occurred in the third trimester of pregnancy and in women residing in urban than rural areas. Chills and rigors, arthralgia, retro-orbital pain, anemia, and vaginal bleeding were more commonly associated with DENV positivity. Backache, arthralgia, jaundice, and vaginal bleeding were more common in CHIKV positives but the difference between positives and nonpositives regarding these symptoms was not statistically significant. Dengue infections were associated with more frequent hospitalizations (OR = 8.38, 95% confidence intervals [CI] = 3.29–21.30) and mortality (OR = 19.0, 95% CI = 1.01–357.10). Hence, to conclude, in India wherever possible, all symptomatic pregnant women should be screened for DENV, CHIKV, and ZIKV as part of sentinel surveillance for ZIKV.

Background Aedes albopictus and Aedes japonicus, two invasive mosquito species in the United States, are implicated in the transmission of arboviruses. Studies have shown interactions of these two mosquito species with a variety of vertebrate hosts; however, regional differences exist and may influence their contribution to arbovirus transmission. Methods We investigated the distribution, abundance, host interactions, and West Nile virus infection prevalence of Ae. albopictus and Ae. japonicus by examining Pennsylvania mosquito and arbovirus surveillance data for the period between 2010 and 2018. Mosquitoes were primarily collected using gravid traps and BG-Sentinel traps, and sources of blood meals were determined by analyzing mitochondrial cytochrome b gene sequences amplified in PCR assays. Results A total of 10,878,727 female mosquitoes representing 51 species were collected in Pennsylvania over the 9-year study period, with Ae. albopictus and Ae. japonicus representing 4.06% and 3.02% of all collected mosquitoes, respectively. Aedes albopictus was distributed in 39 counties and Ae. japonicus in all 67 counties, and the abundance of these species increased between 2010 and 2018. Models suggested an increase in the spatial extent of Ae. albopictus during the study period, while that of Ae. japonicus remained unchanged. We found a differential association between the abundance of the two mosquito species and environmental conditions, percent development, and median household income. Of 110 Ae. albopictus and 97 Ae. japonicus blood meals successfully identified to species level, 98% and 100% were derived from mammalian hosts, respectively. Among 12 mammalian species, domestic cats, humans, and white-tailed deer served as the most frequent hosts for the two mosquito species. A limited number of Ae. albopictus acquired blood meals from avian hosts solely or in mixed blood meals. West Nile virus was detected in 31 pools (n = 3582 total number of pools) of Ae. albopictus and 12 pools (n = 977 total pools) of Ae. japonicus. Conclusions Extensive distribution, high abundance, and frequent interactions with mammalian hosts suggest potential involvement of Ae. albopictus and Ae. japonicus in the transmission of human arboviruses including Cache Valley, Jamestown Canyon, La Crosse, dengue, chikungunya, and Zika should any of these viruses become prevalent in Pennsylvania. Limited interaction with avian hosts suggests that Ae. albopictus might occasionally be involved in transmission of arboviruses such as West Nile in the region. Graphical Abstract

Purpose The present study was undertaken with the objective to study the common etiology of Viral Haemorrhagic Fever (VHF) among patients attending tertiary health care centre in NE India and also to study the clinico-demographic profile of such patients. The agents of VHF included in the study were dengue, chikungunya and Crimean Congo haemorrhagic fever (CCHF) virus. The inclusion of CCHF was based on evidence of seroprevalence in livestock (bovine, sheep and goat) in various North Eastern states. Materials and methods Serum samples were collected from 51 suspected VHF patients. MAC-ELISA was done to detect dengue and chikungunya specific IgM antibody. The samples were also tested by real-time RT-PCR for detection of dengue, chikungunya and CCHF specific nucleic acid. The laboratory and clinico-demographic profile of these patients were noted in detail. Results Serum samples of 16 of 51 suspected cases were confirmed to be suffering from VHF. Among these confirmed cases, 12 were diagnosed with dengue haemorrhagic fever, one was diagnosed with chikungunya and three were diagnosed with dengue-chikungunya co-infection. Based on severity, DHF was further classified into- DHF I- (4,26.6%), DHF II (6,40%), DHF III (3,20%) and DHF IV (2,13.3%). There was no CCHFV infection detected in our study. Retro-orbital pain (P ​= ​0.02) and haematocrit level (P ​= ​0.03) were found to be statistically significant. Conclusions This study reiterates the fact that CCHF virus infection is still probably absent in human population of NE India and haemorrhagic symptoms, though rare maybe one of the atypical manifestations of chikungunya infection.

Background Chikungunya virus (CHIKV) is a re-emerging arbovirus associated with sporadic outbreaks in Cameroon since 2006. Viral whole genomes were generated to analyze the origins of evolutionary lineages, the potential of emergence/re-emergence, and to infer transmission dynamics of recent Cameroon CHIKV outbreak strains. Methods Samples collected between 2016 and 2019 during CHIKV outbreaks in Cameroon were screened for CHIKV using reverse transcription PCR (RT-PCR), followed by whole genome sequencing of positive samples. Results Three coding-complete CHIKV genomes were obtained from samples, which belong to an emerging sub-lineage of the East/Central/South African genotype and formed a monophyletic taxon with previous Central African strains. This clade, which we have named the new Central African clade, appears to be evolving at 3.0 × 10−4 nucleotide substitutions per site per year (95% highest posterior density (HPD) interval of 1.94 × 10−4 to 4.1 × 10−4). Notably, mutations in the envelope proteins (E1-A226V, E2-L210Q, and E2-I211T), which are known to enhance CHIKV adaptability and infectious potential in Aedes albopictus, were present in all strains and mapped to established high-density Ae. albopictus populations. Conclusions These new CHIKV strains constitute a conserved genomic pool of an emerging sub-lineage, reflecting a putative vector host adaptation to Ae. albopictus, which has practically displaced Aedes aegypti from select regions of Cameroon.

Prevention of emerging infections in children is a dynamic arena where substantial medical advances have enabled intervention and prevention of infection outbreaks. This article discusses 5 infections causing significant morbidity and mortality across Asia, Latin America, and Africa. Avian influenza and the Middle East respiratory syndrome are highly contagious zoonoses spread through aerosol and droplets, affecting predominantly Asia. Dengue infection and chikungunya are endemic mosquito-borne viruses in tropical regions across Asia, Latin America, and Africa. Ebola is a highly contagious virus spread through human-to-human contact. The latest information in clinical manifestations, infection, prevention control, chemoprophylaxis, vaccination, and public health measures is reviewed.

Recently, the incidences of chikungunya, dengue and Zika infections have increased due to globalization and urbanization. It is vital that reliable detection tools become available to assess the viral prevalence within mosquito populations.Based on the previous publications on clinical diagnosis in human infections, for the first time, we described a customized triplex RT-qPCR protocol for simultaneous detection of chikungunya virus (CHIKV), dengue virus serotypes 1-4 (DENV1-4) and Zika virus (ZIKV) in mosquitoes.In preliminary assessment to determine the specificity and sensitivity of primers and probes, all six targets were detected individually with the following thresholds as indicated by calculated pfu equivalents: 3.96x10This triplex RT-qPCR assay appears to consistently detect all six targets and does not cross react with Ae. aegypti homogenate, making it a feasible, practical, and immediately adoptable protocol for use among vector control and other entities, particularly in the endemic areas of CHIKV, DENVs and ZIKV.

Background Persistent rheumatic symptoms and its impact on health-related quality of life (QoL), induced by the Indian Ocean Lineage (IOL) chikungunya virus (CHIKV) genotype have been widely studied. In 2014, a major CHIKV outbreak of the Asian genotype occurred in Curaçao, after which we established a longitudinal cohort in 2015, to follow the long-term CHIKV sequalae. Currently, the long-term clinical manifestations and its impact on QoL induced by the Asian CHIKV genotype, followed prospectively through time, and the association of age and comorbidities with rheumatic symptoms persistence, 60 months (M60) after disease onset is unknown. Methods The cohort of 304 laboratory confirmed patients were followed prospectively in time at 3–16 months (M3-16), 30 months (M30), and M60 after disease onset. Demographic and clinical characteristics, and the 36-item short-form survey (SF-36) QoL status were collected through questionnaires. At M60, QoL scores were compared to general population (CHIK-) norms. Results A total of 169 (56%) patients participated (74.6% female, mean age 56.1 years) at all time points, 107 (63%) were classified as recovered and 62 (37%) as affected. The affected patients reported an increase in the prevalence of arthralgia (P .001) and arthralgia in the lower extremities (P Conclusions Rheumatic and non-rheumatic symptoms, and QoL impairment may persist, 60 months following infection with the Asian CHIKV genotype, similar to the IOL genotype disease sequelae. Further research is needed to follow the clinical manifestations and QoL impact of each CHIKV genotype.

Chikungunya virus (CHIKV) belongs to the genus Alphaviridae, with a single-stranded positive-sense RNA genome of 11.8 kbp encoding a polyprotein that generates both non-structural proteins and structural proteins. The virus is transmitted by the Aedes aegypti and A. albopictus mosquitoes, depending on the location. CHIKV infection leads to dengue-like musculoskeletal symptoms and has been responsible for several outbreaks worldwide since its discovery in 1952. Patients often experience fever, headache, muscle pain, joint swelling, and skin rashes. However, the ultrastructural and mechanical properties of CHIKV have not been fully characterized. Thus, this study aims to apply a physical approach to investigate CHIKV′s ultrastructural morphology and mechanical properties, using atomic force microscopy and Raman spectroscopy as the main tools. Using nanomechanical assays of AFM and a gold nanoparticles substrate for Raman signal enhancement, we explored the conformational plasticity, morphology, vibrational signature, and nanomechanical properties of the chikungunya virus, providing new information on its ultrastructure at the nanoscale and offering a novel understanding of the virus’ behavior upon mechanical disruptions besides its molecular composition.

Background/Objective The effects of Chikungunya virus (CHIKV) infection on patients with rheumatic diseases have not been extensively studied. Our aim was to compare the clinical course of patients with rheumatoid arthritis and spondyloarthritis, categorized according to the use or not of biologic disease modifying anti-rheumatic drugs (bDMARDs), during and after infection by CHIKV. Methods Patients from a northeastern Brazilian city that suffered an epidemic outbreak of Chikungunya fever (CHIK) between Oct 2015 and Jul 2016, on regular follow-up in a longitudinal registry of rheumatic patients (BiobadaBrasil), were invited to participate. Participants underwent a standardized clinical interview and collection of blood sample for serological tests (IgM/IgG) for CHIKV. A positive IgG was considered evidence of previous CHIKV infection. Results 105 patients (84 with rheumatoid arthritis, 17 with ankylosing spondylitis, and 4 with psoriatic arthritis) were evaluated. Most patients (58, 55.2%) were on therapy with bDMARDs. The overall prevalence of seropositivity for CHIKV was 47.6% (39.7% in patients on bDMARDs and 57.4% in those exclusively on conventional synthetic (cs-) DMARDs (p = 0.070). Among seropositive patients, asymptomatic disease had similar frequency in those treated and not treated with bDMARDs (39.1% versus 33.3%, respectively; p = 0.670). However, patients exclusively on csDMARDs presented significantly higher prevalence of articular symptoms beyond 3 months and switched treatment more often than patients on bDMARDs (p Conclusions Among rheumatic patients with CHIK, those on bDMARDs had shorter persistence of articular symptoms and switched treatment scheme less often than patients exclusively treated with csDMARDs.

Human retroelements (HERVs) are retroviral origin sequences fixed in the human genome. HERVs induction is associated with neurogenesis, cellular development, immune activation, and neurological disorders. Arboviruses are often associated with the development of encephalitis. The interplay between these viruses and HERVs has not been fully elucidated. In this work, we analyzed RNAseq data derived from infected human primary astrocytes by Zika (ZikV), Mayaro (MayV), Oropouche (OroV) and Chikungunya (ChikV) viruses, and evaluated the modulation of HERVs and their nearby genes. Our data show common HERVs expression modulation by both alphaviruses, suggesting conserved evolutionary routes of transcription regulation. A total of 15 HERVs were co-modulated by the four arboviruses, including the highly upregulated HERV4_4q22. Data on the upregulation of genes nearby to these elements in ChikV, MayV and OroV infections were also obtained, and interaction networks were built. The upregulation of 14 genes common among all viruses was observed in the networks, and 93 genes between MayV and ChikV. These genes are related to cellular processes such as cellular replication, cytoskeleton, cell vesicle traffic and antiviral response. Together, our results support the role of HERVs induction in the transcription regulation process of genes during arboviral infections.

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus. In infected cells, its positive-sense RNA genome is translated into polyproteins that are subsequently processed into four nonstructural proteins (nsP1 to 4), the virus-encoded subunits of the RNA replicase. However, for RNA replication, interactions between nsPs and host proteins are also needed. These interactions are mostly mediated through the intrinsically disordered C-terminal hypervariable domain (HVD) in nsP3. Duplicate FGDF motifs in the HVD are required for interaction with mammalian RasGAP SH3-binding proteins (G3BPs) and their mosquito homolog Rin; these interactions are crucial for CHIKV RNA replication. In this study, we inactivated G3BP/Rin-binding motifs in the HVD and inserted peptides containing either native or inactivated G3BP/Rin-binding motifs into flexible regions of nsP1, nsP2, or nsP4. Insertion of native motifs into nsP1 or nsP2 but not into the C terminus of nsP4 activated CHIKV RNA replication in human cells in a G3BP-dependent manner. In mosquito cells, activation also resulted from the insertion of inactive motifs after residue 8 or 466 in nsP2; however, the effect was significantly larger when the inserted sequence contained native motifs. Nonetheless, CHIKV mutants harboring mutations in the HVD and containing insertions of native motifs in nsP2 were not viable in mosquito cells. In contrast, mutant genomes containing native motifs after residue 466 or 618 in nsP2 replicated in BHK-21 cells, with the latter mutant forming infectious progeny. Thus, the binding of G3BPs to nsP2 can support CHIKV RNA replication and restore the infectivity of viruses lacking G3BP-binding motifs in the HVD of nsP3. IMPORTANCE CHIKV is a reemerging alphavirus that has spread throughout more than 60 countries and is the causative agent of chikungunya fever. No approved drugs or vaccines are available for the treatment or prevention of CHIKV infection. CHIKV replication depends on the ability of its replicase proteins to interact with host cell factors, and a better understanding of host cell factor roles in viral infection will increase our understanding of CHIKV RNA replication and provide new strategies for viral infection attenuation. Here, we demonstrate that the motifs required for the binding of host G3BP/Rin proteins remain functional when transferred from their natural location in nsP3 to different replicase proteins and may enable mutant viruses to complete a full replication cycle. To our knowledge, this is the first demonstration of interaction motifs for crucial host factors being successfully transferred from one replicase protein to another subunit of alphavirus replicase.

Chikungunya virus (CHIKV) is a mosquito-borne emerging pathogen that is transmitted to humans through the bite of female Aedes mosquitoes. CHIKV infection has become a major public health concern worldwide, as it has a significant impact on the healthcare system. Since 2004, the virus has emerged in Africa and subsequently spread to countries located near the Indian Ocean, including India, and to Europe, the Americas, and Asia. In Thailand, a large CHIKV outbreak occurred during 2008-2009 and was caused by a virus originating from the east/central/south African (ECSA) CHIKV genotype. Since then, the ECSA genotype of CHIKV has continued to circulate and has caused sporadic cases in different areas in Thailand. Approximately 20,000 reported cases have been confirmed by the Bureau of Epidemiology, Ministry of Public Health, Thailand, from January 1, 2018 to July 31, 2020. However, the causes of this CHIKV re-emergence remain unclear. To obtain a better understanding of CHIKV circulation during the recent outbreak in Bangkok, Thailand, complete genome analysis of CHIKV isolates from field-caught mosquitoes collected in outbreak areas was performed. A total of 28 Ae. aegypti samples (21 females and 7 males) were collected, and individual mosquitoes were used for CHIKV detection and isolation. Eleven of 28 (39.29%) female and three of 28 (10.71%) male mosquitoes were positive for CHIKV by E1 nested RT-PCR. Four CHIKV isolates were successfully isolated from four female Ae. aegypti mosquitoes. Based on complete genome analysis, several amino acid substitutions were identified in the protein coding region. The E1:K211E and E2:V264A mutations in the background of the E1:226A mutation were observed in all four CHIKV isolates. An important observation was the presence of one amino acid substitution, leading to an E1:K245R change. This mutation was found in all four CHIKV isolates from mosquitoes in this study and in Thai patients described previously. Additionally, phylogenetic analysis indicated that the four CHIKV isolates belonged to the Indian Ocean clade of the ECSA genotype. The results obtained in this study provide detailed information on the molecular characteristics and evolution of currently circulating CHIKV strains in Thailand, which are useful for developing prevention and control strategies.

Chikungunya fever is an acute infectious disease caused by the chikungunya virus (CHIKV) that is characterized by fever, rash, and joint pain. CHIKV has infected millions of people in Africa, Asia, America, and Europe since it re-emerged in the Indian Ocean region in 2004. Here, we report an outbreak of Chikungunya fever that occurred in Ruili of Yunnan Province, a city located on the border between China and Myanmar, in September 2019. The outbreak lasted for three months from September to December. Overall, 112 cases were confirmed by a real-time reverse-transcription polymerase chain reaction in the Ruili People's Hospital, and they showed apparent temporal, spatial, and population aggregation. Among them, 91 were local cases distributed in 19 communities of Ruili City, and 21 were imported cases. The number of female patients was higher than that of male patients, and most patients were between 20 and 60 years old. The main clinical manifestations included joint pain (91.96%), fever (86.61%), fatigue (58.04%), chills (57.14%), rash (48.21%), headache (39.29%), and so forth. Biochemical indexes revealed increased C-reactive protein (63.39%), lymphopenia (57.17%), increased hemoglobin (33.04%), neutrophilia (28.57%), and thrombocytopenia (16.07%). Phylogenetic analysis of the complete sequences indicated that the CHIKV strains in this outbreak belonged to the Indian Ocean clade of the East/Central/South African genotype. We speculated that this chikungunya outbreak might be caused by CHIKV-infected persons returning from Myanmar, and provided a reference for the formulation of effective treatment and prevention measures.