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Abstract Background Long-term chikungunya disease, characterized by persistent disabling rheumatic symptoms, including poly-arthralgia/arthritis of severe pain intensity, can persist for years after infection with the re-emerging mosquito-borne chikungunya virus. Although persistent symptoms and pain severity are important determinants of health-care seeking and self-management of symptoms, research on these in relation to long-term chikungunya disease is scarce. This study aimed to explore the perceived benefits and perceived barriers concerning health-care seeking, based on the Health Belief Model, and the symptoms self-management strategies used for health outcome improvement among individuals affected by long-term chikungunya disease. Methods An exploratory qualitative descriptive study was conducted with 20 purposively selected adults (17 females and 3 males) with persistent rheumatic symptoms, recruited from an ongoing longitudinal chikungunya cohort, in Curaçao. Semi-structured interviews were carried out, audio-recorded, and transcribed. An iterative coding process was used for themes identification through inductive thematic analyses. Results No perceived benefits in health-care seeking were reported. Identified themes in relation to perceived barriers were: (1) health-care seeking at disease onset; (2) general practitioners (GPs) perceptions and awareness of persistent symptoms; (3) challenges for medical referrals and support; (4) no validation of symptoms and challenges accessing therapy; (5) health system restrictions; and (6) social stigmatization of psychological help. These perceived barriers have led participants to self-manage persistent symptoms. Over-the-counter pharmacological and/or non-pharmacological treatments were used without consulting GPs. Identified themes were: (1) self-medication of symptoms; and (2) self-management true non-pharmacological treatments. Conclusions To promote the benefits of long-term health-care seeking and subsequently reduce the possible harmful use of analgesics, a collaborative physician-patient therapeutic relationship need to be encouraged. To facilitate this, important shifts may be needed in chikungunya sequalae education of both patients and health-care professionals, and policy makers need to revise health systems for the long-term provision of multidisciplinary care to achieve beneficial health outcomes in long-term chikungunya disease.

Sensitive detection of infectious diseases is crucial for effective clinical care. However, commercial rapid tests may be limited in their ability to detect pathogen variants across different countries. It was found that the sensitivity of a chikungunya rapid test on local strain was only 20.5% as compared to the East, Central, and South Africa (ECSA) phylogroup. Therefore, the development of geographically specific diagnostics is essential. Investigating the distinctive structural properties of a locally sourced antigenic protein is an important initiative for the development of a specific antibody. This study utilized structural bioinformatics and molecular dynamics simulations to investigate the differences between the E1-E2 antigenic proteins of the Indonesian chikungunya virus (Ind-CHIKV) and that of ECSA. The results showed that some of the mutation points are located at the antibody binding sites of Ind-CHIKV. G194S and V318R mutations were proposed as distinctive features of Ind-CHIKV, leading to weaker antibody binding compared to ECSA. It suggests that modifying the antibody to accommodate bulkier side chains at positions 194 and 318 could improve its effectiveness against Ind-CHIKV. These insights are valuable for developing a highly sensitive immunoassay for Ind-CHIKV and other regional pathogens, ultimately enhancing diagnostic capabilities in Indonesia.

Viral-borne diseases have recently gained significant public health importance in the current world. The Viral Research and Diagnostic Laboratory (VRDL) located at Government Theni Medical College (GTMC), Theni, Tamil Nadu, conducts the diagnosis of common virus infections. The purpose of this study is to investigate the seroprevalence of dengue (DENV) and chikungunya (CHIKV) virus infections, as well as their co-infection, in people who have clinical symptoms. From January 2018 to June 2023, serum samples were collected from clinically suspected patients at the tertiary care hospital in Theni, Tamil Nadu. DENV and CHIKV were detected using an enzyme-linked immunosorbent assay (ELISA) in all of the samples. A total of 16,997 cases were enrolled, out of which 11264/2971(26.3%) tested positive for Dengue IgM, 1395/288 (20.6%) for Dengue NS1 Ag, 19/3(15.7%) for IgG, followed by 4319/3388(8.9%) of CHIKV IgM. Fever (n = 16598, 97.6%) was the most prevalent clinical characteristic in all probable dengue and chikungunya patients. Other symptoms were chills (n = 11252, 66.1%), arthralgia (n = 10245, 60.2%), headache (n = 11354, 66.8%), and joint pain (n = 11256, 66.2%). The findings showed a lesser likelihood of acquiring both DENV and CHIKV infections at the same time; however, the risk is still not trivial. This study investigates the clinical presentation of Dengue-Chikungunya patients. The rising prevalence of dengue and chikungunya, as well as their co-infection, need thorough monitoring of endemic areas and good patient care management.

The co-circulation of chikungunya virus (CHIKV), dengue virus (DENV) and Zika virus (ZIKV) in Rio de Janeiro (RJ), Brazil, caused a challenging triple epidemic, as they share similar clinical signs and symptoms and geographical distribution. Here, we aimed to investigate the clinical and laboratorial aspects of chikungunya suspected cases assisted in RJ during the 2018 outbreak, focusing on the differential diagnosis with dengue and zika. All suspected cases were submitted to molecular and/or serological differential diagnostic approaches to arboviruses. A total of 242 cases suspected of arbovirus infection were investigated and 73.6% (178/242) were molecular and/or serologically confirmed as chikungunya. In RT-qPCR confirmed cases, cycle threshold (Ct) values ranged from 15.46 to 35.13, with acute cases presenting lower values. Chikungunya cases were mainly in females (64%) and the most frequently affected age group was adults between 46 to 59 years old (27%). Polyarthralgia affected 89% of patients, especially in hands and feet. No dengue virus (DENV) and Zika virus (ZIKV) infections were confirmed by molecular diagnosis, but 9.5% (23/242) had serological evidence of DENV exposure by the detection of specific anti-DENV IgM or NS1, and 42.7% (76/178) of chikungunya positive cases also presented recent DENV exposure reflected by a positive anti-DENV IgM or NS1 result. A significantly higher frequency of arthritis (p = 0.023) and limb edema (p < 0.001) was found on patients with CHIKV monoinfection compared to dengue patients and patients exposed to both viruses. Lastly, phylogenetic analysis showed that the chikungunya cases were caused by the ECSA genotype. Despite the triple arboviruses epidemic in the state of RJ, most patients with fever and arthralgia investigated here were diagnosed as chikungunya cases, and the incidence of CHIKV/DENV co-detection was higher than that reported in other studies.

ObjectiveChikungunya virus (CHIKV) causes persistent arthritis, and our prior study showed that approximately one third of CHIKV arthritis patients had exacerbated arthritis associated with exercise. The underlying mechanism of exercise-associated chikungunya arthritis flare (EACAF) is unknown, and this analysis aimed to examine the regulatory T-cell immune response related to CHIKV arthritis flares.MethodsIn our study, 124 Colombian patients with a history of CHIKV infection four years prior were enrolled and 113 cases with serologically confirmed CHIKV IgG were used in this analysis. Patient information was gathered via questionnaires, and blood samples were taken to identify total live peripheral blood mononuclear cells, CD4+ cells, T regulatory cells, and their immune markers. We compared outcomes in CHIKV patients with (n = 38) vs. without (n = 75) EACAF using t-tests to assess means and the Fisher's exact test, chi-squared to evaluate categorical variables, and Kruskal-Wallis tests in the setting of skewed distributions (SAS 9.3).Results33.6% of CHIKV cases reported worsening arthritis with exercise. EACAF patients reported higher global assessments of arthritis disease ranging from 0-100 (71.2 ± 19.7 vs. 59.9 ± 28.0, p=0.03). EACAF patients had lower ratios of T regulatory (Treg)/CD4+ T-cells (1.95 ± 0.73 vs. 2.4 ± 1.29, p = 0.04) and lower percentage of GARP (glycoprotein-A repetitions predominant) expression per Treg (0.13 ± 0.0.33 vs. 0.16 ± 0.24 p= 0.020).ConclusionThese findings suggest relative decreases in GARP expression may indicate a decreased level of immune suppression. Treg populations in patients with CHIKV arthritis may contribute to arthritis flares during exercise, though current research is conflicting.

The article discusses the growing concern of arboviral diseases such as dengue and chikungunya in travelers. The United States has recently approved the world's first chikungunya vaccine, which has shown promising results in terms of seroresponse and clinical benefit. The article also highlights the increasing incidence of dengue in travelers and the availability of a new dengue vaccine. The recommendations for the use of these vaccines vary among different expert groups, but the authors argue for broader recommendations to address the high burden of these diseases. Further research is needed to gather more data on the vaccines' effectiveness, safety, and duration of protection. [Extracted from the article]

Paraguay is currently facing a new outbreak of Chikungunya virus. This report summarizes two severe cases of Chikungunya (CHIKV) infection, confirmed by real-time reverse transcription polymerase chain reaction. We present the cases of patients with acute CHIKV infection and multisystem involvement, with fever, rash, abdominal pain, vomiting, myocarditis, and coronary artery anomalies, very similar to the cases described in MIS-C related to SARS-CoV-2 during the COVID-19 Pandemic. Both patients received IVIG and methylprednisolone, with good clinical response. In this setting of cytokine storm in Chikungunya, can we call it "Multisystem inflammatory syndrome associated with Chikungunya"?. [ABSTRACT FROM AUTHOR]

Arboviruses such as dengue, Zika, and chikungunya present similar symptoms in the early stages, which complicates their differential and timely diagnosis. In 2022, the PAHO published a guide to address this challenge. This study proposes a methodological framework that transforms qualitative information into quantitative information, establishing differential weights in relation to symptoms according to the medical evidence and the GRADE scale based on recommendation 1 of the said guide. To achieve this, common variables from the dataset were identified using the PAHO guide, and quality rules were established. A linear interpolation function was then parameterised to assign weights to the symptoms according to the evidence. Machine learning was used to compare the different models, achieving 99% accuracy compared with 79% without the methodology. This proposal represents a significant advancement, allowing the direct application of the PAHO recommendations to the dataset and improving the differential classification of arboviruses.

Background: Chikungunya, a resurging vector-borne disease caused by chikungunya virus, remains a global health challenge. In 2023, globally 4.4 lakhs suspected cases and 365 fatalities were estimated; India accounting for 21% of the global burden. On 5 September 2023, suspected outbreak of chikungunya was reported at Bolasa village, Jhabua, Madhya Pradesh by local newspaper. Objective: We investigated to confirm the outbreak, describe the epidemiology and provide evidence-based recommendations. Methodology: We compared past three years Integrated Disease Surveillance System (IDSP) data to confirm the outbreak. We defined a suspect case as fever with arthralgia in a resident of Bolasa village, during 20 August-30 October 2023, searched cases by reviewing patients register from health-care-facilities and house-to-house in Bolasa village. Cases were interviewed using semi- structured questionnaire prepared by modifying WHO chikungunya toolbox and data analyzed using Microsoft-Excel. We conducted environmental survey at domestic and peri-domestic areas and serum samples collected for laboratory confirmation. Results: No chikungunya case was reported in the last three years. We identified 117 suspected cases (56% females) with median age of 40 years (range 27-52 years). Other than fever and arthralgia, the other symptoms included bodyache (78%) and headache (67%). Overall attack rate (AR) was 8%; highest AR in Tadvifaliya of 18% followed by Harijan and Patidar faliya with 12% each. Among the cases, 76% stored water in containers without cover, mosquito larvae were found in the containers in the house or nearby place of 60% cases. Of the 20 serum samples tested, nine were positive for chikungunya IgM-antibody. Conclusion: We detected a confirmed chikungunya outbreak in a rural setting with vector breeding sites identified in a community. Outbreak investigation led to vector control by eliminating breeding sites and community sensitization on water storage practices. We recommended early case reporting, periodic entomological surveys and source reduction.

Abstract Background Accurate case report data are essential to understand arbovirus dynamics, including spread and evolution of arboviruses such as Zika, dengue and chikungunya viruses. Giving the multi-country nature of arbovirus epidemics in the Americas, these data are not often accessible or are reported at different time scales (weekly, monthly) from different sources. Results We developed a publicly available and user-friendly database for arboviral case data in the Americas: ARCA. ARCA is a relational database that is hosted on the ARCA website. Users can interact with the database through the website by submitting queries through the website, which generates displays results and allows users to download these results in different, convenient file formats. Users can choose to view arboviral case data through a table which containscontaining the number of cases for a particular week, a plot, or through a map. Conclusion Our ARCA database is a useful tool for arboviral epidemiology research allowing for complex queries, data visualization, integration, and formatting.

The chikungunya virus (CHIKV) has produced epidemic outbreaks of significant public health impact. The clinical symptoms of this disease are fever, polyarthralgia, and skin rash, generally self-limiting, although patients may develop a chronic disabling condition or suffer lethal complications. Unfortunately, there is no specific treatment or vaccine available. Thus, the search for effective therapies to control CHIKV infection is an urgent need. This study evaluated the antiviral activity of flavonoids isolated from Marcetia taxifolia by in vitro and in silico analysis. Cytotoxicity of compounds was determined by MTT assay and viral load was assessed in cell substrates supernatants by plaque-forming and RT-qPCR assays. Selected molecules were analyzed by molecular docking assays. Myricetin 3-rhamnoside (MR) and myricetin 3-(6-rhamnosylgalactoside) (MRG) were tested for antiviral assays and analyzed by the TCID50 method and RT-qPCR. MR exhibited dose-dependent antiviral activity, reducing viral titer at concentrations of 150-18.8 μg/mL by at least 1-log. Similarly, MRG showed a significant decrease in viral titer at concentrations of 37.5, 9.4, and 2.3 μg/mL. RT-qPCR analysis also displayed a substantial reduction of CHIKV RNA for both flavonoids. Furthermore, molecular docking of the selected flavonoids proposed the nsP3 macrodomain as a possible target of action. Our study reveals that MR and MRG could be considered promising anti-CHIKV therapeutic agents. Molecular modeling studies showed MR and MRG ligands with a high affinity for the N-terminal region of the nsP3 macrodomain, postulating them as a potential target of action for the CHIKV control.

Abstract Background Chikungunya is associated with high morbidity and the natural history of symptomatic infection has been divided into three phases (acute, post-acute, and chronic) according to the duration of musculoskeletal symptoms. Although this classification has been designed to help guide therapeutic decisions, it does not encompass the complexity of the clinical expression of the disease and does not assist in the evaluation of the prognosis of severity nor chronic disease. Thus, the current challenge is to identify and diagnose musculoskeletal disorders and to provide the optimal treatment in order to prevent perpetuation or progression to a potentially destructive disease course. Methods The study is the first product of the Clinical and Applied Research Network in Chikungunya (REPLICK). This is a prospective, outpatient department-based, multicenter cohort study in Brazil. Four work packages were defined: i. Clinical research; ii) Translational Science – comprising immunology and virology streams; iii) Epidemiology and Economics; iv) Therapeutic Response and clinical trials design. Scheduled appointments on days 21 (D21) ± 7 after enrollment, D90 ± 15, D120 ± 30, D180 ± 30; D360 ± 30; D720 ± 60, and D1080 ± 60 days. On these visits a panel of blood tests are collected in addition to the clinical report forms to obtain data on socio-demographic, medical history, physical examination and questionnaires devoted to the evaluation of musculoskeletal manifestations and overall health are performed. Participants are asked to consent for their specimens to be maintained in a biobank. Aliquots of blood, serum, saliva, PAXgene, and when clinically indicated to be examined, synovial fluid, are stored at -80° C. The study protocol was submitted and approved to the National IRB and local IRB at each study site. Discussion Standardized and harmonized patient cohorts are needed to provide better estimates of chronic arthralgia development, the clinical spectra of acute and chronic disease and investigation of associated risk factors. This study is the largest evaluation of the long-term sequelae of individuals infected with CHIKV in the Brazilian population focusing on musculoskeletal manifestations, mental health, quality of life, and chronic pain. This information will both define disease burden and costs associated with CHIKV infection, and better inform therapeutic guidelines.

Abstract Background Dengue, Chikungunya, and Zika are co-endemic in Honduras and are often misdiagnosed due to similar clinical and epidemiological behavior. Most arboviral infections reported in primary care are based on clinical diagnoses without laboratory confirmation. Therefore, the accuracy of physicians’ diagnoses and the factors that affect them needs to be evaluated. Methods A cross-sectional study with convenience sampling at primary healthcare centers was conducted from June to September 2016 and 2017. Clinical data and dried blood spots on Whatman 903 filter paper from 415 arboviral cases and 248 non-arboviral febrile cases were collected. Viral RNA was extracted from a 6-mm DBS paper disc and confirmed by RT-qPCR and sequencing. Results Only 30.84% of diagnostic accuracy was observed in physicians in primary care when comparing arboviral clinical diagnosis with RT-qPCR detection. Moreover, in Dengue and Zika clinical cases, only 8.23% and 27.08% were RT-qPCR confirmed, respectively. No Chikungunya cases were confirmed. In 2017, 20.96% of febrile cases were RT-qPCR confirmed arboviral infections. The symptoms of 45.5% of arboviral cases can fit more than one case definition for arboviruses. The “symptom compliance” and “patient with suspected close contact” were the criteria most utilized by physicians for arboviral diagnosis. The pattern of the epidemiological curves of the arboviral clinical cases didn’t match the one of the RT-qPCR confirmed cases. Conclusions Low diagnostic accuracy for overall and individual arboviral infections was observed in physicians. Unspecific symptomatology, overlapping case definitions, and reported close contact to an arboviral patient might contribute to misdiagnosis. Without laboratory confirmation, surveillance data may not reflect the real behavior of these diseases and could impact health interventions.

Chikungunya fever is an arboviral disease caused by the Chikungunya virus (CHIKV), which is classified into three genotypes, namely Asian, West African, and East/Central/South African (ECSA). Due to the frequency and severity of CHIKV outbreaks, it is crucial to genetically characterize the virus, especially in non-endemic regions. This report describes a case and genome characterization of CHIKV from a case that was detected in Jeddah (in 2021) during the COVID-19 pandemic. CHIKV was identified in a 32-year-old male patient in Jeddah, originally from India, who presented with fever, myalgia, malaise, and fatigue and was initially suspected of having dengue. The patient had no history of travel in the fortnight prior to his presentation. Treatment included paracetamol, saline, and vitamin C, which is important for the host immune response and detoxification of viral products. The genome of CHIKV was sequenced using various techniques and bioinformatics tools. Amino acid mutations were studied. Phylogenetic analysis showed that the CHIKV strain detected in 2021 was genetically distinct from those reported in 2018. The 2021 virus shared ancestry with CHIKV strains reported in India. This strain possessed E1-K211E, E2-V264A, and E1-I317V mutations. Novel substitutions were identified. The CHIKV re-emergence in 2021 in Jeddah belonged to the Indian subcontinent/Southeast Asia clade of ECSA. More molecular epidemiological information is needed to better understand and evaluate the prevalence of CHIKV in Saudi Arabia.

Abstract Background and Aim Severe morbidity and mortality due to seasonal infectious diseases are common global public health issues. Vector‐borne viral illnesses like dengue and chikungunya overload the healthcare systems leading to critical financial burden to manage them. There is no effective drug or vaccine currently available to control these two diseases. Methods The review was formulated by incorporating relevant reports on chikungunya and dengue in the Americas regions through a comprehensive search of literature that were available on dedicated scientific publication portals such as PubMed, ScienceDirect, and Web of Science. Results The strategies of public health administrations to control largely the mosquito vectors during tropical monsoon seem to be effective. Yet, it seems practically impossible to completely eliminate them. The mosquito vector disseminates the virus via transovarian route thereby internalising the virus through generations, a reason behind reappearing and recurring outbreaks. The numerous factors associated with industrialisation, urbanisation, population density, and easy transboundary movements appear to have contributed to the spread of vectors from an endemic region to elsewhere. Conclusion The article made a state‐of‐affair comprehensive analysis of the rising dengue and chikungunya cases in the tropics, particularly the tropical Americas, as a human health concern, the countermeasures undertaken and the overall preparedness. The viral transmission is a hard situation to tackle as the vector survives in diverse temperature and ecology, is resistant to insecticides, and the unavailability of drugs. Better vector‐control measures and improved understanding of the reemerging arboviral infections could offer an extended reaction time to counter outbreaks, and minimise associated morbidity/mortality.

Chikungunya virus (CHIKV) and Dengue virus (DENV) are vector-borne diseases transmitted by Aedes aegypti and Aedes albopictus that pose a significant threat to global public health. Cases of acute Chikungunya fever often present similar clinical symptoms to other vector-borne diseases, such as Dengue fever. In regions where multiple vector-borne diseases coexist, CHIKV is often overlooked or misdiagnosed as Dengue virus, West Nile virus, Zika virus or other viral infections, which delays its prevention and control. However, IgM antibodies directed against the E2 protein of CHIKV have not yet been generalized to clinical settings due to the low sensitivity and high cost in commercial kits. Indirect ELISA with peptides provides an effective supplementary tool for detecting CHIKV IgM antibodies. Our study aims at examining the potential of linear epitopes on the E2 glycoprotein that specifically bind to IgM antibodies as serodiagnostic tool for CHIKV. The sensitivity of the established peptide indirect ELISA method for detecting clinical samples is significantly better than that of commercial kits, realizing a beneficial supplement to the existing IgM antibody assay. It also established the groundwork for comprehending the biological mechanisms of the CHIKV E2 protein and the advancement of innovative epitope peptide vaccines.

This study aimed to analyze the spatial distribution of chikungunya cases in Piauí between 2015 and 2019. This was a spatial ecological study of notified and confirmed cases of chikungunya, with data from the Notifiable Diseases Information System (SINAN) from 2015 to 2019. The X² association test was applied for the bivariate analysis and the spatial analysis was performed from the data treatment to combine with the cartographic base in the free software Qgis (version 3.16.7 Hannover). During this period, 9596 cases and 7950 confirmed cases of chikungunya were reported. The city of Teresina (53.21%) and the health region Entre Rios (58.27%) had the highest records. Females (58.40%), aged between 20 and 34 years (29.63%) and mixed race (50.26%) were the most affected. Regarding education, 56.55% were ignored and, regarding the months of notification, the months of the 1st semester had the highest number of cases (62.8%). Chikungunya cases are concentrated in poles with large population flows. In this way, the identification of the epidemiological profile, as well as its main risk factors, is a way of helping the health system of the entire state in the elaboration of specific control policies for the population most vulnerable to the disease.

ABSTRACT Chikungunya fever (CHIK) is a neglected tropical disease associated with chronic arthritis. CHIK is usually a self-limiting condition; however, extra-articular manifestations present as atypical illness in a minority of patients. These atypical features may mimic other conditions and potentially distract physicians from the true diagnosis. This review analyzes the evidence of many unusual extra-articular manifestations reported in cases of CHIK. Depending on the affected system, these unusual manifestations include encephalitis, myocarditis, acute interstitial nephritis, cutaneous manifestations, acute anterior uveitis, abdominal pain, and depression. In addition, coinfections and comorbidities may cause atypical illness and obscure the diagnosis. Further studies are required to clarify the pathophysiology and natural history of CHIK, as it remains a burdening condition. Exploring its atypical symptoms may be the missing scientific piece of this puzzle.

Assessing the factors responsible for differences in outbreak severity for the same pathogen is a challenging task, since outbreak data are often incomplete and may vary in type across outbreaks (e.g., daily case counts, serology, cases per household). We propose that outbreaks described with varied data types can be directly compared by using those data to estimate a common set of epidemiological parameters. To demonstrate this for chikungunya virus (CHIKV), we developed a realistic model of CHIKV transmission, along with a Bayesian inference method that accommodates any type of outbreak data that can be simulated. The inference method makes use of the fact that all data types arise from the same transmission process, which is simulated by the model. We applied these tools to data from three real-world outbreaks of CHIKV in Italy, Cambodia, and Bangladesh to estimate nine model parameters. We found that these populations differed in several parameters, including pre-existing immunity and house-to-house differences in mosquito activity. These differences resulted in posterior predictions of local CHIKV transmission risk that varied nearly fourfold: 16% in Italy, 28% in Cambodia, and 62% in Bangladesh. Our inference method and model can be applied to improve understanding of the epidemiology of CHIKV and other pathogens for which outbreaks are described with varied data types.

The burden of vector-borne infections is significant, particularly in low- and middle-income countries where vector populations are high and healthcare infrastructure may be inadequate. Further, studies are required to investigate the key factors of vector-borne infections to provide effective control measure. This study focuses on formulating a mathematical framework to characterize the spread of chikungunya infection in the presence of vaccines and treatments. The research is primarily dedicated to descriptive study and comprehension of dynamic behaviour of chikungunya dynamics. We use Banach's and Schaefer's fixed point theorems to investigate the existence and uniqueness of the suggested chikungunya framework resolution. Additionally, we confirm the Ulam–Hyers stability of the chikungunya system. To assess the impact of various parameters on the dynamics of chikungunya, we examine solution pathways using the Laplace-Adomian method of disintegration. Specifically, to visualise the impacts of fractional order, vaccination, bite rate and treatment computer algorithms are employed on the infection level of chikungunya. Our research identified the framework's essential input settings for managing chikungunya infection. Notably, the intensity of chikungunya infection can be reduced by lowering mosquito bite rates in the affected area. On the other hand, vaccination, memory index or fractional order, and treatment could be used as efficient controlling variables. [ABSTRACT FROM AUTHOR]

It is significant to investigate the transmission dynamics of vector-borne infection because it has a global impact, can help predict and prevent future outbreaks, is important for understanding the impact of climate change on public health, can lead to more effective control strategies, and can improve our comprehension of the dynamics of these infections. Our paper presents a new model for chikungunya virus infection, which considers treatment and vaccination, using the Atangana-Baleanu derivative within the framework of the Caputo definition. First of all, we examine the positivity and uniqueness of the solution for the model. Then, we find out the fundamental results of the suggested model, such as the steady-state without infection and the R 0 value that indicates endemicity pertaining to the system. Furthermore, we verify the local asymptotic stability of the infection-free steady-state. Through the application of fixed-point theory, we demonstrate the existence of the solution and propose a numerical methodology to investigate the dynamic behavior of the model. Finally, we performed simulations to demonstrate the effects of vaccination, transmission probability, treatment, and index of memory on the system's solution pathways. The findings of this research suggest the most sensitive parameters of the system responsible for the control and prevention of the infection. Emphasizing the significance of the memory index as an attractive parameter, we propose its consideration to the policy makers as a control parameter for the prevention of the infection. [ABSTRACT FROM AUTHOR]

Chikungunya fever (CHIKF) has re-emerged in the southernmost Thailand and presents a significant threat to public health. The problem areas can be identified using appropriate statistical models. This study aimed to determine the geographic epidemic patterns and high-risk locations. Data on CHIKF's case characteristics, including age, gender, and residence sub-district, were obtained from the Office of Disease Prevention and Control of Thailand from 2008 to 2020. A logistic model was applied to detect illness occurrences. After removing records with no cases, a log-linear regression model was used to determine the incidence rate. The results revealed that two large-scale infections occurred in the southernmost provinces of Thailand between 2008 and 2010, and again between 2018 and 2020, indicating a 10-year epidemic cycle. The CHIKF occurrence in the first and second outbreaks was 28.4% and 15.5%, respectively. In both outbreaks of occurrence CHIKF, adolescents and working-age groups were the most infected groups but the high incidence rate of CHIKF was elderly groups. The first outbreak had a high occurrence and incidence rate in 39 sub-districts, the majority of which were in Narathiwat province, whilst the second outbreak was identified in 15 sub-districts, the majority of which were in Pattani province. In conclusion, the CHIKF outbreak areas can be identified and addressed by combining logistic and log-linear models in a two-step process. The findings of this study can serve as a guide for developing a surveillance strategy or an earlier plan to manage or prevent the CHIKF outbreak. [ABSTRACT FROM AUTHOR]

Chikungunya virus is an arbovirus that causes the neglected tropical disease chikungunya fever, common in tropical areas worldwide. There is evidence that arboviruses alter host transcriptome and modulate immune response; this modulation may involve transcriptional and post-transcriptional control mechanisms mediated by long non-coding RNAs (lncRNAs). Herein, we employed bioinformatic analysis to evaluate co-expression of lncRNAs and their putative target mRNAs in whole blood during natural Chikungunya infection in adolescent boys. Sequencing data from GSE99992 was uploaded to the Galaxy web server, where data was aligned with HISAT2, gene counts were estimated with HTSeq-count, and differential expression was run with DESeq2. After gene classification with Biomart, Pearson's correlation was applied to identify potential interactions between lncRNAs and mRNAs, which were later classified into cis and trans according to genomic location (FEELnc) and binding potential (LncTar), respectively. We identified 1,975 mRNAs and 793 lncRNAs that were differentially expressed between the acute and convalescent stages of infection in the blood. Of the co-expressed lncRNAs and mRNAs, 357 potentially interact in trans and 9 in cis; their target mRNAs enriched pathways related to immune response and viral infections. Out of 52 enriched KEGG pathways, the RIG-I like receptor signaling is enriched by the highest number of target mRNAs. This pathway starts with the recognition of viral pathogens, leading to innate immune response mediated by the production of IFN-I and inflammatory cytokines. Our findings indicate that alterations in lncRNA expression in adolescent boys, induced by acute Chikungunya infection, potentially modulate mRNAs that contribute to antiviral immune responses. [ABSTRACT FROM AUTHOR]

Chikungunya fever (CHIF), a vector-borne disease transmitted mainly by Aedes albopictus and Aedes aegypti, is caused by Chikungunya virus (CHIKV) infection. To date, it is estimated that 39% of the world's population is at risk of infection for living in countries and regions where CHIKV is endemic. However, at present, the cellular receptors of CHIKV remains not clear, and there are no specific drugs and vaccines for CHIF. Here, the cytotoxicity of calpain-2 protein activity inhibitor III and specific siRNA was detected by MTT assays. The replication of CHIKV was detected by qPCR amplification and plaque assay. Western blot was used to determine the level of the calpain-2 protein and vimentin protein. Immunofluorescence was also operated for detecting the rearrangement of vimentin protein. Our results indicated that calpain-2 protein activity inhibitor III and specific siRNA might suppress CHIKV replication. Furthermore, CHIKV infection led to vimentin remodeling and formation of cage-like structures, which could be inhibited by the inhibitor III. In summary, we confirmed that calpain-2 protein influenced chikungunya virus replication and regulated vimentin rearrangement caused by chikungunya virus infection, which could be important for understanding the biological significance of CHIKV replication and the future development of antiviral strategies. [ABSTRACT FROM AUTHOR]

Background: Paraguay has recently experienced an exponential increase in chikungunya cases, leading to psychological distress, particularly anxiety. Aim: To develop and validate the Chikungunya Anxiety Scale (CHIKAS). Materials and Methods: An initial scale of 18 items was used, which was subjected to validation by expert judgment to obtain 14 items. To determine construct validity, exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) have been employed, and internal and convergent validity were determined. Demographic, socioeconomic, and health status data were also collected. Results: The study included 974 participants. The final scale consisted of 12 items with evidence of a two-factor model (psychological and physical). The internal validity was good (McDonald’s omega = 0.882). The CFA showed good adjustment indices. Regarding participant characteristics, a relationship was found between anxiety due to chikungunya and gender, employment, mental diagnosis, medication use, and chikungunya infection. Conclusion: The final 12‑item CHIKAS had strong psychometric properties and was a two-factor model. [ABSTRACT FROM AUTHOR]

Chikungunya virus (CHIKV) is an arthropod-transmitted Alphavirus endemic to countries in Africa and Asia, including Indonesia, which causes debilitating arthralgia which can last several years. The rapid spread of CHIKV to new areas makes the discovery of antiviral agents a high priority. α-mangostin is a xanthone from mangosteen (Garcinia mangostana) pericarp and has antiviral activity against Hepatitis C and Dengue viruses. We investigated the antiviral activity of α-mangostin against CHIKV in HepG2 cells in pre-, post- and combination treatments compared to the common antiviral medicine ribavirin, as well their cytotoxicity. Our results show dose-responsive reductions in viral titer in all treatment regimes, with post- and combination treatments being more effective than pre-treatment only (IC50 = 7.79, 5.99 and 6.39 μM, respectively), but with poor specificity (SI = 1.39, 1.81 and 1.70, respectively) compared to ribavirin. Neither compound showed a direct virucidal effect. These results suggest α-mangostin effectively inhibits CHIKV replication in this cell line. [ABSTRACT FROM AUTHOR]

Chikungunya fever, a debilitating disease caused by Chikungunya virus (CHIKV), is characterized by a high fever of sudden onset and an intense arthralgia that impairs individual regular activities. Although most symptoms are self-limited, long-term persistent arthralgia is observed in 30–40% of infected individuals. Currently, there is no vaccine or specific treatment against CHIKV infection, so there is an urgent need for the discovery of new therapeutic options for CHIKF chronic cases. This present study aims to test the antiviral, cytoprotective, and anti-inflammatory activities of an ethanol extract (FF72) from Ampelozizyphus amazonicus Ducke wood, chemically characterized using mass spectrometry, which indicated the major presence of dammarane-type triterpenoid saponins. The major saponin in the extract, with a deprotonated molecule ion m/z 897 [M-H]−, was tentatively assigned as a jujubogenin triglycoside, a dammarane-type triterpenoid saponin. Treatment with FF72 resulted in a significant reduction in both virus replication and the production of infective virions in BHK-21-infected cells. The viability of infected cells was assessed using an MTT, and the result indicated that FF72 treatment was able to revert the toxicity mediated by CHIKV infection. In addition, FF72 had a direct effect on CHIKV, since the infectivity was completely abolished in the presence of the extract. FF72 treatment also reduced the expression of the major pro-inflammatory mediators overexpressed during CHIKV infection, such as IL-1β, IL-6, IL-8, and MCP-1. Overall, the present study elucidates the potential of FF72 to become a promising candidate of herbal medicine for alphaviruses infections. [ABSTRACT FROM AUTHOR]

Alphaviruses are serious zoonotic threats responsible for significant morbidity, causing arthritis or encephalitis. So far, no licensed drugs or vaccines are available to combat alphaviral infections. About 300,000 chikungunya virus (CHIKV) infections have been reported in 2023, with more than 300 deaths, including reports of a few cases in the USA as well. The discovery and development of small-molecule drugs have been revolutionized over the last decade. Here, we employed a cell-based screening approach using a series of in-house small-molecule libraries to test for their ability to inhibit CHIKV replication. DCR 137, a quinazoline derivative, was found to be the most potent inhibitor of CHIKV replication in our screening assay. Both, the cytopathic effect, and immunofluorescence of infected cells were reduced in a dose-dependent manner with DCR 137 post-treatment. Most importantly, DCR 137 was more protective than the traditional ribavirin drug and reduced CHIKV plaque-forming units by several log units. CHIKV-E2 protein levels were also reduced in a dose-dependent manner. Further, DCR 137 was probed for its antiviral activity against another alphavirus, the Ross River virus, which revealed effective inhibition of viral replication. These results led to the identification of a potential quinazoline candidate for future optimization that might act as a pan-alphavirus inhibitor. [ABSTRACT FROM AUTHOR]

Alphavirus infections cause multiple alterations in the intracellular environment that can have both positive and negative effects on viral replication. The Old World alphaviruses, such as Sindbis (SINV), chikungunya (CHIKV), and Semliki Forest viruses, hinder the ability of vertebrate cells to form stress granules (SGs). Previously, this inhibitory function was attributed to the hypervariable domain (HVD) of nsP3, which sequesters the key SG components, G3BP1 and G3BP2, and to the nsP3 macro domain. The macro domain possesses ADP-ribosylhydrolase activity, which can diminish the ADP-ribosylation of G3BP1 during viral replication. However, our recent findings do not support the prevailing notions. We demonstrate that the interactions between SINV- or CHIKV-specific nsP3s and G3BPs, and the ADP-ribosylhydrolase activity are not major contributors to the inhibitory process, at least when nsP3 is expressed at biologically relevant levels. Instead, the primary factors responsible for suppressing SG formation are virus-induced transcriptional and translational shutoffs that rapidly develop within the first few hours post infection. Poorly replicating SINV variants carrying mutated nsP3 HVD still inhibit SG development even in the presence of sodium arsenite (NaAs). Conversely, SINV mutants lacking transcription and/or translation inhibitory functions lose their ability to inhibit SG formation, despite expressing high levels of wt nsP3. Moreover, we found that stable cell lines expressing GFP-nsP3 fusions retain the capacity to form SGs when exposed to NaAs. However, our results do not rule out the possibility that additional alphavirus-induced changes in cell biology may contribute to the suppression of SG formation. [ABSTRACT FROM AUTHOR]

Dengue et chikungunya représentent un problème de santé publique majeur touchant à la fois les régions tropicales, avec une incidence en nette augmentation, mais également les régions tempérées, avec la description de transmissions autochtones pendant la période d'activité des moustiques vecteurs. Ces deux infections virales se caractérisent par une incubation courte avant l'apparition d'une sympto-matologie similaire, généralement constituée d'un syndrome pseudo-grippal et d'une éruptio-n maculo-papuleuse. Elles se distinguent toutefois par leurs compli-cations constituées, pour la dengue, de formes hémorragiques engageant le pronostic vital et, pour le chikungunya, de formes invalidantes par le passage à la chronicité des douleurs articulaires. Dans les deux cas, le diagnostic virologique repose sur la mise en évidence précoce du génome viral et la détection plus tardive des anticorps. Enfin, il n'existe pas de traitement spéci-fique mais des mesures prophylactiques sont possibles associant vaccination (dengue) et protection individuelle et collective anti-moustique. En conclusion, dengue et chikungunya représentent deux arboviroses à fort potentie-l d'émergence dans les pays tempérés par l'expansion du moustique tigre et l'intensification des voyages. Leur recherche en cas de signes cliniques évocateurs chez un individu n'ayant jamais voyagé est vraisemblablement une attitude qu'il faudra systématiquement adopter en période estivale dans un futur proche. Dengue fever and chikungunya represent a major public health problem affecting both tropical regions, with an increasing incidence, but also temperate regions, with the description of autochthonous transmissions during the period of activity of mosquito vectors. These two viral infections are characterized by a short incubation period before the appearance of similar symptomatology, generally consisting of an influenza-like illness and a maculopapular rash. However, they are distinguished by their complications consisting, for dengue, of hemorrhagic forms involving the vital prognosis and, for chikungunya, of disabling forms due to the chronicity of joint pain. In both cases, virological diagnosis is based on the early detection of the viral genome and the later detection of antibodies. Finally, there is no specific treatment but prophylactic measures are possible combining vaccination (dengue fever) and, individual and collective anti-mosquito protection. In conclusion, dengue fever and chikungunya represent two arboviruses with high potential for emergence in temperate countries by the expansion of the tiger mosquito and the intensification of travel. Their search in case of suggestive clinical signs in an individual who has never traveled is probably an attitude that will have to be systematically adopted during the summer period in the near future. [ABSTRACT FROM AUTHOR]

A surge in chikungunya was observed during 2020‐21 in Pune district of Maharashtra, India. Whole genome sequencing and phylogenetic analysis of 21 samples/sequences revealed them as Indian ocean lineage of East Central South African genotype. Two distinct sequence clusters were found to circulate during 2020‐21; one with E1:K211E and E2:V264A mutations while the other had E1:I317V mutation along with E1:K211E and E2: V264A mutations. The former, the predominant cluster (n = 18), clustered with chikungunya virus (CHIKV) strains of pre 2014 period while the latter (n = 3) clustered with 2016−2018 period Indian strains. Though E1: A226V was not detected in any of the 21 sequences, several unique mutations were detected in the strains which might have played key roles in the enhanced virus transmission during the period. The study highlights parallel evolution, introduction from the neighboring regions and cocirculation of two sequence clusters of CHIKV in Pune. The complete genome data can be useful to determine how the circulating strains differ from candidate vaccines and might help to predict the protective efficacy of chikungunya vaccine candidates. [ABSTRACT FROM AUTHOR]

The Delphi technique is a qualitative technique which consists of a series of systematic steps to combine the knowledge and opinion of experts regarding a specific topic and reach a consensus as a means of scenario building and forecasting. This technique is rarely used in tourism, albeit it has been recommended since 1990 (Green, H., Hunter, C., & Moore, B. [1990]. Assessing the environmental impact of tourism development: Use of the Delphi technique. Tourism Management, 11(2), 111–120). The goal of this research note is to demonstrate use of the Delphi technique as a means of building a richer depth of understanding about the likelihood of a Chikungunya outbreak and the impact to the tourism industry. [ABSTRACT FROM AUTHOR]

Temperature is a well-known effector of several transmission factors of mosquito-borne viruses, including within mosquito dynamics. These dynamics are often characterized by vector competence and the extrinsic incubation period (EIP). Vector competence is the intrinsic ability of a mosquito population to become infected with and transmit a virus, while EIP is the time it takes for the virus to reach the salivary glands and be expectorated following an infectious bloodmeal. Temperatures outside the optimal range act on life traits, decreasing transmission potential, while increasing temperature within the optimal range correlates to increasing vector competence and a decreased EIP. These relatively well-studied effects of other Aedes borne viruses (dengue and Zika) are used to make predictions about transmission efficiency, including the challenges presented by urban heat islands and climate change. However, the knowledge of temperature and chikungunya (CHIKV) dynamics within its two primary vectors—Ae. aegypti and Ae. albopictus—remains less characterized, even though CHIKV remains a virus of public-health importance. Here, we review the literature and summarize the state of the literature on CHIKV and temperature dependence of vector competence and EIP and use these data to demonstrate how the remaining knowledge gap might confound the ability to adequately predict and, thus, prepare for future outbreaks. [ABSTRACT FROM AUTHOR]

Chikungunya virus (CHIKV) is transmitted to humans by mosquitoes of the genus Aedes, causing the chikungunya fever disease, associated with inflammation and severe articular incapacitating pain. There has been a worldwide reemergence of chikungunya and the number of cases increased to 271,006 in 2022 in the Americas alone. The replication of CHIKV takes place in several cell types, including phagocytic cells. Monocytes and macrophages are susceptible to infection by CHIKV; at the same time, they provide protection as components of the innate immune system. However, in host–pathogen interactions, CHIKV might have the ability to alter the function of immune cells, partly by rewiring the tricarboxylic acid cycle. Some viral evasion mechanisms depend on the metabolic reprogramming of immune cells, and the cell metabolism is intertwined with circadian rhythmicity; thus, a circadian immunovirometabolism axis may influence viral pathogenicity. Therefore, analyzing the interplay between viral infection, circadian rhythmicity, and cellular metabolic reprogramming in human macrophages could shed some light on the new field of immunovirometabolism and eventually contribute to the development of novel drugs and therapeutic approaches based on circadian rhythmicity and metabolic reprogramming. [ABSTRACT FROM AUTHOR]

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Chikungunya and Zika have been neglected as emerging diseases. This study aimed to analyze the space-time patterns of their occurrence and co-occurrence and their associated environmental and socioeconomic factors. Univariate (individually) and multivariate (co-occurrence) scans were analyzed for 608,388 and 162,992 cases of chikungunya and Zika, respectively. These occurred more frequently in the summer and autumn. The clusters with the highest risk were initially located in the northeast, dispersed to the central-west and coastal areas of São Paulo and Rio de Janeiro (2018–2021), and then increased in the northeast (2019–2021). Chikungunya and Zika demonstrated decreasing trends of 13% and 40%, respectively, whereas clusters showed an increasing trend of 85% and 57%, respectively. Clusters with a high co-occurrence risk have been identified in some regions of Brazil. High temperatures are associated with areas at a greater risk of these diseases. Chikungunya was associated with low precipitation levels, more urbanized environments, and places with greater social inequalities, whereas Zika was associated with high precipitation levels and low sewage network coverage. In conclusion, to optimize the surveillance and control of chikungunya and Zika, this study's results revealed high-risk areas with increasing trends and priority months and the role of socioeconomic and environmental factors. [ABSTRACT FROM AUTHOR]

Background: Aedes (Stegomyia)-borne diseases are an expanding global threat, but gaps in surveillance make comprehensive and comparable risk assessments challenging. Geostatistical models combine data from multiple locations and use links with environmental and socioeconomic factors to make predictive risk maps. Here we systematically review past approaches to map risk for different Aedes-borne arboviruses from local to global scales, identifying differences and similarities in the data types, covariates, and modelling approaches used. Methods: We searched on-line databases for predictive risk mapping studies for dengue, Zika, chikungunya, and yellow fever with no geographical or date restrictions. We included studies that needed to parameterise or fit their model to real-world epidemiological data and make predictions to new spatial locations of some measure of population-level risk of viral transmission (e.g. incidence, occurrence, suitability, etc.). Results: We found a growing number of arbovirus risk mapping studies across all endemic regions and arboviral diseases, with a total of 176 papers published 2002–2022 with the largest increases shortly following major epidemics. Three dominant use cases emerged: (i) global maps to identify limits of transmission, estimate burden and assess impacts of future global change, (ii) regional models used to predict the spread of major epidemics between countries and (iii) national and sub-national models that use local datasets to better understand transmission dynamics to improve outbreak detection and response. Temperature and rainfall were the most popular choice of covariates (included in 50% and 40% of studies respectively) but variables such as human mobility are increasingly being included. Surprisingly, few studies (22%, 31/144) robustly tested combinations of covariates from different domains (e.g. climatic, sociodemographic, ecological, etc.) and only 49% of studies assessed predictive performance via out-of-sample validation procedures. Conclusions: Here we show that approaches to map risk for different arboviruses have diversified in response to changing use cases, epidemiology and data availability. We identify key differences in mapping approaches between different arboviral diseases, discuss future research needs and outline specific recommendations for future arbovirus mapping. [ABSTRACT FROM AUTHOR]

Chikungunya virus (CHIKV) is an alphavirus transmitted by mosquitos that causes a debilitating disease characterized by fever and long-lasting polyarthralgia. To date, no vaccine has been licensed, but multiple vaccine candidates are under evaluation in clinical trials. One of these vaccines is based on a measles virus vector encoding for the CHIKV structural genes C, E3, E2, 6K, and E1 (MV-CHIK), which proved safe in phase I and II clinical trials and elicited CHIKV-specific antibody responses in adult measles seropositive vaccine recipients. Here, we predicted T-cell epitopes in the CHIKV structural genes and investigated whether MV-CHIK vaccination induced CHIKV-specific CD4+ and/or CD8+ T-cell responses. Immune-dominant regions containing multiple epitopes in silico predicted to bind to HLA class II molecules were found for four of the five structural proteins, while no such regions were predicted for HLA class I. Experimentally, CHIKV-specific CD4+ T-cells were detected in six out of twelve participants after a single MV-CHIK vaccination and more robust responses were found 4 weeks after two vaccinations (ten out of twelve participants). T-cells were mainly directed against the three large structural proteins C, E2 and E1. Next, we sorted and expanded CHIKV-specific T cell clones (TCC) and identified human CHIKV T-cell epitopes by deconvolution. Interestingly, eight out of nine CD4+ TCC recognized an epitope in accordance with the in silico prediction. CHIKV-specific CD8+ T-cells induced by MV-CHIK vaccination were inconsistently detected. Our data show that the MV-CHIK vector vaccine induced a functional transgene-specific CD4+ T cell response which, together with the evidence of neutralizing antibodies as correlate of protection for CHIKV, makes MV-CHIK a promising vaccine candidate in the prevention of chikungunya. [ABSTRACT FROM AUTHOR]

In a phase 2 safety and immunogenicity study of a chikungunya virus virus-like particle (CHIKV VLP) vaccine in an endemic region, of 400 total participants, 78 were found to be focus reduction neutralizing antibody seropositive at vaccination despite being ELISA seronegative at screening, of which 39 received vaccine. This post hoc analysis compared safety and immunogenicity of CHIKV VLP vaccine in seropositive (n = 39) versus seronegative (n = 155) vaccine recipients for 72 weeks post-vaccination. There were no differences in solicited adverse events, except injection site swelling in 10.3% of seropositive versus 0.6% of seronegative recipients (p = 0.006). Baseline seropositive vaccine recipients had stronger post-vaccination luciferase neutralizing antibody responses versus seronegative recipients (peak geometric mean titer of 3594 and 1728, respectively) persisting for 72 weeks, with geometric mean fold increases of 3.1 and 13.2, respectively. In this small study, CHIKV VLP vaccine was well-tolerated and immunogenic in individuals with pre-existing immunity. ClinicalTrials.gov Identifier: NCT02562482. [ABSTRACT FROM AUTHOR]

The true risk for many travel diseases is unknown because most studies do not detect asymptomatic infections. In this study, we performed ELISA for dengue virus (DENV), chikungunya virus (CHIKV), Zika virus (ZIKV), hepatitis E virus (HEV), and Campylobacter jejuni on samples from 81 healthy Germans before and after they traveled to Asia. ELISA found five seroconversions for C. jejuni, two for DENV, one for ZIKV, and zero for HEV. For CHIKV, three subjects were positive before travel and negative afterwards. None had symptoms. These infections would have gone unnoticed by retrospective studies. Therefore, the risk for these infections may be higher than previously estimated. [ABSTRACT FROM AUTHOR]