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Chikungunya virus (CHIKV) a mosquito-borne alphavirus is the causative agent of Chikungunya (CHIK), a disease with low mortality but high acute and chronic morbidity resulting in a high overall burden of disease. After the acute disease phase, chronic disease including persistent arthralgia is very common, and can cause fatigue and pain that is severe enough to limit normal activities. On average, around 40% of people infected with CHIKV will develop chronic arthritis, which may last for months or years. Recommendations for protection from CHIKV focus on infection control through preventing mosquito proliferation. There is currently no licensed antiviral drug or vaccine against CHIKV. Therefore, one of the most important public health impacts of vaccination would be to decrease burden of disease and economic losses in areas impacted by the virus, and prevent or reduce chronic morbidity associated with CHIK. This benefit would particularly be seen in Low and Middle Income Countries (LMIC) and socio-economically deprived areas, as they are more likely to have more infections and more severe outcomes. This 'Vaccine Value Profile' (VVP) for CHIK is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic and societal value of vaccines in the development pipeline and vaccine-like products. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships, and multi-lateral organizations. All contributors have extensive expertise on various elements of the CHIK VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information. [ABSTRACT FROM AUTHOR]

Chikungunya is an arboviral disease transmitted by Aedes aegypti and Aedes albopictus mosquitoes with a growing global burden linked to climate change and globalisation. We aimed to estimate chikungunya seroprevalence, force of infection (FOI), and prevalence of related chronic disability and hospital admissions in endemic and epidemic settings. In this systematic review, meta-analysis, and modelling study, we searched PubMed, Ovid, and Web of Science for articles published from database inception until Sept 26, 2022, for prospective and retrospective cross-sectional studies that addressed serological chikungunya virus infection in any geographical region, age group, and population subgroup and for longitudinal prospective and retrospective cohort studies with data on chronic chikungunya or hospital admissions in people with chikungunya. We did a systematic review of studies on chikungunya seroprevalence and fitted catalytic models to each survey to estimate location-specific FOI (ie, the rate at which susceptible individuals acquire chikungunya infection). We performed a meta-analysis to estimate the proportion of symptomatic patients with laboratory-confirmed chikungunya who had chronic chikungunya or were admitted to hospital following infection. We used a random-effects model to assess the relationship between chronic sequelae and follow-up length using linear regression. The systematic review protocol is registered online on PROSPERO, CRD42022363102. We identified 60 studies with data on seroprevalence and chronic chikungunya symptoms done across 76 locations in 38 countries, and classified 17 (22%) of 76 locations as endemic settings and 59 (78%) as epidemic settings. The global long-term median annual FOI was 0·007 (95% uncertainty interval [UI] 0·003–0·010) and varied from 0·0001 (0·00004–0·0002) to 0·113 (0·07–0·20). The highest estimated median seroprevalence at age 10 years was in south Asia (8·0% [95% UI 6·5–9·6]), followed by Latin America and the Caribbean (7·8% [4·9–14·6]), whereas median seroprevalence was lowest in the Middle East (1·0% [0·5–1·9]). We estimated that 51% (95% CI 45–58) of people with laboratory-confirmed symptomatic chikungunya had chronic disability after infection and 4% (3–5) were admitted to hospital following infection. We inferred subnational heterogeneity in long-term average annual FOI and transmission dynamics and identified both endemic and epidemic settings across different countries. Brazil, Ethiopia, Malaysia, and India included both endemic and epidemic settings. Long-term average annual FOI was higher in epidemic settings than endemic settings. However, long-term cumulative incidence of chikungunya can be similar between large outbreaks in epidemic settings with a high FOI and endemic settings with a relatively low FOI. International Vaccine Institute. [ABSTRACT FROM AUTHOR]

Chikungunya virus outbreaks have been associated with excess deaths at the ecological level. Previous studies have assessed the risk factors for severe versus mild chikungunya virus disease. However, the risk of death following chikungunya virus disease compared with the risk of death in individuals without the disease remains unexplored. We aimed to investigate the risk of death in the 2 years following chikungunya virus disease. We used a population-based cohort study and a self-controlled case series to estimate mortality risks associated with chikungunya virus disease between Jan 1, 2015, and Dec 31, 2018, in Brazil. The dataset was created by linking national databases for social programmes, notifiable diseases, and mortality. For the matched cohort design, individuals with chikungunya virus disease recorded between Jan 1, 2015, and Dec 31, 2018, were considered as exposed and those who were arbovirus disease-free and alive during the study period were considered as unexposed. For the self-controlled case series, we included all deaths from individuals with a chikungunya virus disease record, and each individual acted as their own control according to different study periods relative to the date of disease. The primary outcome was all-cause natural mortality up to 728 days after onset of chikungunya virus disease symptoms, and secondary outcomes were cause-specific deaths, including ischaemic heart diseases, diabetes, and cerebrovascular diseases. In the matched cohort study, we included 143 787 individuals with chikungunya virus disease who were matched, at the day of symptom onset, to unexposed individuals using sociodemographic factors. The incidence rate ratio (IRR) of death within 7 days of chikungunya symptom onset was 8·40 (95% CI 4·83–20·09) as compared with the unexposed group and decreased to 2·26 (1·50–3·77) at 57–84 days and 1·05 (0·82–1·35) at 85–168 days, with IRR close to 1 and wide CI in the subsequent periods. For the secondary outcomes, the IRR of deaths within 28 days after disease onset were: 1·80 (0·58–7·00) for cerebrovascular diseases, 3·75 (1·33–17·00) for diabetes, and 3·67 (1·25–14·00) for ischaemic heart disease, and there was no evidence of increased risk in the subsequent periods. For the self-controlled case series study, 1933 individuals died after having had chikungunya virus disease and were included in the analysis. The IRR of all-cause natural death within 7 days of symptom onset of chikungunya virus disease was 8·75 (7·18–10·66) and decreased to 1·59 (1·26–2·00) at 57–84 days and 1·09 (0·92–1·29) at 85–168 days. For the secondary outcomes, the IRRs of deaths within 28 days after disease onset were: 2·73 (1·50–4·96) for cerebrovascular diseases, 8·43 (5·00–14·21) for diabetes, and 2·38 (1·33–4·26) for ischaemic heart disease, and there was no evidence of increased risk at 85–168 days. Chikungunya virus disease is associated with an increased risk of death for up to 84 days after symptom onset, including deaths from cerebrovascular diseases, ischaemic heart diseases, and diabetes. This study highlights the need for equitable access to approved vaccines and effective anti-chikungunya virus therapeutics and reinforces the importance of robust vector-control efforts to reduce viral transmission. Brazilian National Research Council (CNPq), Fundação de Amparo à Pesquisa do Estado da Bahia, Wellcome Trust, and UK Medical Research Council. For the Portuguese translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

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]

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]

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]

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]

Printed electronic technologies have sparked interest worldwide because of their capacity to transcend the limitations of existing high-cost electronics based on the fabrication of various devices deploying flexible substrates. Fabricating electrodes on stretchable, bendable, and soft substrates plays a vital role in flexible electronics. Hence this study demonstrates an electrochemical flexible substrate-based aptamer sensor for the Chikungunya virus (CHIKV) antigen over an extensive range of concentrations. In brief, ZnO nanorods were chemically synthesised and characterised by Field emission scanning electron microscopy (FESEM), UV-Vis spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, and X-Ray Diffraction (XRD), providing biocompatibility to the aptamer, a biorecognition element. The aptasensor showed a wide linearity (1 ng/ml-10 μg/ml), deploying a voltammetric identification in the presence of 10 mM methylene blue act as a redox-transition substance, with an estimated limit of detection of 1 ng/ml and 25 s as its optimal response time. The applicability of the sensor was further demonstrated by introducing CHIKV-Antigen into commercial serum samples. The built-in sensor has a shelf-life of approximately a month. CHIKV-Antigen can be detected rapidly on a portable platform. As a result, CHIKV can be diagnosed more quickly, allowing for more effective treatment choices. [Display omitted] • In-house, a flexible glove based three electrode system was developed. • Chemically synthesized and thoroughly characterized zinc oxide nanorods were utilized. • The built electrochemical sensor performed in human serum efficiently. • This sensor could be used to diagnose Chikungunya virus antigen. • The application of the Dengue Virus protein confirmed cross-reactivity. [ABSTRACT FROM AUTHOR]

Mosquito-transmitted chikungunya virus (CHIKV) is the causal pathogen of CHIKV disease and is responsible for global epidemics of arthritic disease. CHIKV infection can lead to severe chronic and debilitating arthralgia, significantly impacting patient mobility and quality of life. Our previous studies have shown a live-attenuated CHIKV vaccine candidate, CHIKV-NoLS, to be effective in protecting against CHIKV disease in mice vaccinated with one dose. Further studies have demonstrated the value of a liposome RNA delivery system to deliver the RNA genome of CHIKV-NoLS directly in vivo, promoting de novo production of live-attenuated vaccine particles in vaccinated hosts. This system, designed to bypass live-attenuated vaccine production bottlenecks, uses CAF01 liposomes. However, one dose of CHIKV-NoLS CAF01 failed to provide systemic protection against CHIKV challenge in mice, with low levels of CHIKV-specific antibodies. Here we describe CHIKV-NoLS CAF01 booster vaccination regimes designed to increase vaccine efficacy. C57BL/6 mice were vaccinated with three doses of CHIKV-NoLS CAF01 either intramuscularly or subcutaneously. CHIKV-NoLS CAF01 vaccinated mice developed a systemic immune response against CHIKV that shared similarity to vaccination with CHIKV-NoLS, including high levels of CHIKV-specific neutralising antibodies in subcutaneously inoculated mice. CHIKV-NoLS CAF01 vaccinated mice were protected against disease signs and musculoskeletal inflammation when challenged with CHIKV. Mice given one dose of live-attenuated CHIKV-NoLS developed a long lasting protective immune response for up to 71 days. A clinically relevant CHIKV-NoLS CAF01 booster regime can overcome the challenges faced by our previous one dose strategy and provide systemic protection against CHIKV disease. [ABSTRACT FROM AUTHOR]

Chikungunya, a mosquito-borne viral disease caused by the chikungunya virus (CHIKV), causes a significant global health burden, and there is currently no approved vaccine to prevent chikungunya disease. In this study, the safety and immunogenicity of a CHIKV mRNA vaccine candidate (mRNA-1388) were evaluated in healthy participants in a CHIKV-nonendemic region. This phase 1, first-in-human, randomized, placebo-controlled, dose-ranging study enrolled healthy adults (ages 18–49 years) between July 2017 and March 2019 in the United States. Participants were randomly assigned (3:1) to receive 2 intramuscular injections 28 days apart with mRNA-1388 in 3 dose-level groups (25 μg, 50 μg, and 100 μg) or placebo and were followed for up to 1 year. Safety (unsolicited adverse events [AEs]), tolerability (local and systemic reactogenicity; solicited AEs), and immunogenicity (geometric mean titers [GMTs] of CHIKV neutralizing and binding antibodies) of mRNA-1388 versus placebo were evaluated. Sixty participants were randomized and received ≥ 1 vaccination; 54 (90 %) completed the study. mRNA-1388 demonstrated favorable safety and reactogenicity profiles at all dose levels. Immunization with mRNA-1388 induced substantial and persistent humoral responses. Dose-dependent increases in neutralizing antibody titers were observed; GMTs (95 % confidence intervals [CIs]) at 28 days after dose 2 were 6.2 (5.1–7.6) for mRNA-1388 25 μg, 53.8 (26.8–108.1) for mRNA-1388 50 μg, 92.8 (43.6–197.6) for mRNA-1388 100 μg, and 5.0 (not estimable) for placebo. Persistent humoral responses were observed up to 1 year after vaccination and remained higher than placebo in the 2 higher mRNA-1388 dose groups. The development of CHIKV-binding antibodies followed a similar trend as that observed with neutralizing antibodies. mRNA-1388, the first mRNA vaccine against CHIKV, was well tolerated and elicited substantial and long-lasting neutralizing antibody responses in healthy adult participants in a nonendemic region. ClinicalTrials.gov : NCT03325075. [ABSTRACT FROM AUTHOR]

In recent decades, there has been an increased interest in developing a vaccine for chikungunya. However, due to its unpredictable transmission, planning for a chikungunya vaccine trial is challenging. To inform decision making on the selection of sites for a vaccine efficacy trial, we developed a new framework for projecting the expected number of endpoint events at a given site. In this framework, we first accounted for population immunity using serological data collated from a systematic review and used it to estimate parameters related to the timing and size of past outbreaks, as predicted by an SIR transmission model. Then, we used that model to project the infection attack rate of a hypothetical future outbreak, in the event that one were to occur at the time of a future trial. This informed projections of how many endpoint events could be expected if a trial were to take place at that site. Our results suggest that some sites may have sufficient transmission potential and susceptibility to support future vaccine trials, in the event that an outbreak were to occur at those sites. In general, we conclude that sites that have experienced outbreaks within the past 10 years may be poorer targets for chikungunya vaccine efficacy trials in the near future. Our framework also generates projections of the numbers of endpoint events by age, which could inform study participant recruitment efforts. [ABSTRACT FROM AUTHOR]

Chikungunya (CHIK) is an underdiagnosed acute febrile illness (AFI) and an important cause of acute encephalitis syndrome (AES). Unavailaibility of rapid and sensitive molecular point-of-care tests (PoCTs) for CHIK at grass-root level, results in increased hospital burden, due to delayed diagnosis or misdiagnosis with other clinically relevant diseases. Since, no therapeutic intervention is readily available, accurate and differential diagnosis of CHIK is the only available option to initiate early supportive treatment. Thus, we aimed to develop a one-pot reverse transcription recombinase polymerase amplification (RT-RPA) mediated CRISPR/Cas12a based detection platform for rapid, specific, and ultrasensitive detection of chikungunya virus (CHIKV) in clinical samples. We have successfully integrated CRISPR/Cas12a technology with reverse transcription recombinase polymerase amplification (RT-RPA) for the detection of Chikungunya virus (CHIKV). The developed assay enabled rapid detection of CHIKV within 35 min, requiring minimal handling process and instrumentation. Next, this assay demonstrated dual mode end-point detection capabilities, employing both fluorescence and lateral flow detection within a reaction. Our one-pot system allows the entire process to be completed without the need to open the reaction tube, thereby eliminating the risk of cross-contamination. Remarkably, the assay exhibits an analytical sensitivity of 412 zg μL−1 (≈1 copy), and 100 % clinical sensitivity and specificity for CHIKV. Furthermore, the developed assay demonstrated limit of detection of 8 gene copies of CHIKV. The assay demonstrates precise detection of CHIKV without any cross-reactivity with other pathogens commonly associated AFI or AES. The overall findings of this study indicate that the RT-RPA:CRISPR/Cas12a detection assay, with one-pot dual-mode detection approach enables rapid, specific and ultrasensitive molecular detection of CHIKV. This advancement holds significant potential for CHIKV detection in resource-limited settings, providing a robust tool for diagnosis and management of the disease. This developed assay may empower clinicians to initiate prompt supportive therapy for Chikungunya fever, thereby improving patient outcomes and public health responses. [Display omitted] • VRACCH integrates RT-RPA with CRISPR/Cas12a for Chikungunya detection. • This method integrated both fluorescence and lateral flow strip end-point detection in single reaction. • One-pot RT-RPA-CRISPR/Cas12a method detected 412 zg μL−1 (≈1 copy) of Chikungunya virus E1 gene. • VRACCH eliminates carryover contamination and facilitates ultrasensitive detection of chikungunya virus. • The assay had demonstrated 100 % clinical sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Chikungunya virus (CHIKV) is responsible for the most endemic alphavirus infections called Chikungunya. The endemicity of Chikungunya has increased over the past two decades, and it is a pathogen with pandemic potential. There is currently no approved direct-acting antiviral to treat the disease. As part of our antiviral drug discovery program focused on alphaviruses and the non-structural protein 2 protease, we discovered that J12 and J13 can inhibit CHIKV nsP2 protease and block the replication of CHIKV in cell cultures. Both compounds are metabolically stable to human liver microsomal and S9 enzymes. J13 has excellent oral bioavailability in pharmacokinetics studies in mice and ameliorated Chikungunya symptoms in preliminary efficacy studies in mice. J13 exhibited an excellent safety profile in in vitro safety pharmacology and off-target screening assays, making J13 and its analogs good candidates for drug development against Chikungunya. [Display omitted] • NsP2 protease inhibitors with antiviral activity were investigated in this work. • Vinyl sulfone-based inhibitors were discovered to be active against Chikungunya virus. • The drug lead J13 has excellent oral bioavailability and off-target selectivity. • The drug lead, J13 , showed promising in vivo efficacy in mouse models. [ABSTRACT FROM AUTHOR]

Background: Introgression of genetic material from species of the insect bacteria Wolbachia into populations of Aedes aegypti mosquitoes has been shown in randomised and non-randomised trials to reduce the incidence of dengue; however, evidence for the real-world effectiveness of large-scale deployments of Wolbachia-infected mosquitoes for arboviral disease control in endemic settings is still scarce. A large Wolbachia (wMel strain) release programme was implemented in 2017 in Rio de Janeiro, Brazil. We aimed to assess the effect of this programme on the incidence of dengue and chikungunya in the city.Methods: 67 million wMel-infected mosquitoes were released across 28 489 locations over an area of 86·8 km2 in Rio de Janeiro between Aug 29, 2017 and Dec 27, 2019. Following releases, mosquitoes were trapped and the presence of wMel was recorded. In this spatiotemporal modelling study, we assessed the effect of the release programme on the incidence of dengue and chikungunya. We used spatiotemporally explicit mathematical models applied to geocoded dengue cases (N=283 270) from 2010 to 2019 and chikungunya cases (N=57 705) from 2016 to 2019.Findings: On average, 32% of mosquitoes collected from the release zones between 1 month and 29 months after the initial release tested positive for wMel. Reduced wMel introgression occurred in locations and seasonal periods in which cases of dengue and chikungunya were historically high, with a decrease to 25% of mosquitoes testing positive for wMel during months in which disease incidence was at its highest. Despite incomplete introgression, we found that the releases were associated with a 38% (95% CI 32-44) reduction in the incidence of dengue and a 10% (4-16) reduction in the incidence of chikungunya.Interpretation: Stable establishment of wMel in the geographically diverse, urban setting of Rio de Janeiro seems to be more complicated than has been observed elsewhere. However, even intermediate levels of wMel seem to reduce the incidence of disease caused by two arboviruses. These findings will help to guide future release programmes.Funding: Bill & Melinda Gates Foundation and the European Research Council. [ABSTRACT FROM AUTHOR]

• Risaralda, Colombia is endemic for Aedes -borne viruses (ABV) like Dengue virus, Zika virus, and Chikungunya virus. • ABV transmission is heterogenous, and future work may identify risk factors. • Most pregnant women in Risaralda are susceptible to Zika infection. • Cord blood is a convenient and efficient sample to achieve public health objectives. Aedes -borne viruses (ABV) affect humans on every inhabited continent and frequently cause epidemics. Recent epidemics of chikungunya and Zika viruses (ZIKV) highlight that preparedness for future epidemics requires assessment of susceptibility, particularly among high-risk groups. We sought to determine immunity against the three major circulating ABV among pregnant women in an ABV-endemic area of Colombia. A cross-sectional seroprevalence study was performed, enrolling women presenting to Labor and Delivery. Cord blood and maternal peripheral blood samples were obtained. IgG seroprevalence to flaviviruses and chikungunya was determined by ELISA. An abbreviated neutralization test was used to estimate the frequency and magnitude of immunity to Zika and four dengue serotypes. Cluster analyses explored epidemiologic factors associated with seroprevalence. Most women exhibited high levels of neutralizing antibodies to one or more ABV; however, nearly 20% were seronegative for flaviviruses. Our research took place after the epidemic peak of the ZIKV outbreak in Colombia in 2016. However, only 20% of pregnant women had high levels of Zika-neutralizing antibodies consistent with likely protective immunity to ZIKV. Hence, a high proportion of pregnant women in Risaralda remain susceptible to one or more ABV including the teratogenic ZIKV, indicating a risk for future epidemics in this region. [ABSTRACT FROM AUTHOR]

• No treatment or chemoprophylaxis exists for chikungunya disease. • Household clustering of chikungunya infections occurs in varied settings. • Antiviral agents can be tested for preventing within-household transmission. • We suggest a practical clinical trial model for a neglected tropical disease. • This model may also be applicable to other mosquito-borne virus diseases. 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. [Display omitted] [ABSTRACT FROM AUTHOR]

Inactivated viral vaccines have long been used in humans for diseases of global health threat (e.g., poliomyelitis and pandemic and seasonal influenza) and the technology of inactivation has more recently been used for emerging diseases such as West Nile, Chikungunya, Ross River, SARS and especially for COVID-19. The Brighton Collaboration Benefit-Risk Assessment of VAccines by TechnolOgy (BRAVATO) Working Group has prepared standardized templates to describe the key considerations for the benefit and risk of several vaccine platform technologies, including inactivated viral vaccines. This paper uses the BRAVATO inactivated virus vaccine template to review the features of an inactivated whole chikungunya virus (CHIKV) vaccine that has been evaluated in several preclinical studies and clinical trials. The inactivated whole CHIKV vaccine was cultured on Vero cells and inactivated by ß-propiolactone. This provides an effective, flexible system for high-yield manufacturing. The inactivated whole CHIKV vaccine has favorable thermostability profiles, compatible with vaccine supply chains. Safety data are compiled in the current inactivated whole CHIKV vaccine safety database with unblinded data from the ongoing studies: 850 participants from phase II study (parts A and B) outside of India, and 600 participants from ongoing phase II study in India, and completed phase I clinical studies for 60 subjects. Overall, the inactivated whole CHIKV vaccine has been well tolerated, with no significant safety issues identified. Evaluation of the inactivated whole CHIKV vaccine is continuing, with 1410 participants vaccinated as of 20 April 2022. Extensive evaluation of immunogenicity in humans shows strong, durable humoral immune responses. [ABSTRACT FROM AUTHOR]

Background: The current practice of child neurology in Latin America has been impacted by the waves of sociopolitical unrest that in the last decades have swept the region.Methods: We searched the available literature referring to the situation of child neurology in Latin America and conditions that specifically impact the region.Results: In lower-middle-income countries, the number of child neurologists is inadequate. Child neurologists working in large public hospitals can only afford to do so on a part-time basis as these institutions are chronically underfunded. Several circumstances are particularly relevant to Latin America: Spanish is the main language spoken, something that limits the opportunity to keep local child neurologists up to date. The structure of health care systems in Latin America varies significantly. Some countries have fragmented systems with inadequate capacity to offer equitable access to medical care. Latin America has been impacted by epidemics of arthropod-borne viruses: zika, chikungunya, and dengue. It stands to reason that the COVID-19 pandemic will affect the distribution of resources for chronic neurological conditions.Conclusions: The virtual platforms such as Zoom, expanded during the COVID-19 pandemic, are useful not only to improve access to care through telemedicine but also for educational purposes. Collaborative efforts to support educational courses and symposia in Spanish are ongoing. It is necessary to set short- and long-term priorities to improve child neurology care in the region. Immediate priorities should focus on improving the diagnosis of neurological conditions, making emphasis on locally available resources. [ABSTRACT FROM AUTHOR]

Chikungunya fever, caused by Chikungunya virus (CHIKV) exhibits clinical features that mimic that of other arbovirus infections such as dengue. CHIKV Envelope 2 (E2) protein, an antigenic epitope of CHIKV, has been identified as an ideal marker for diagnostics. The current CHIKV antigen detection tests are largely based on antibodies but are beleaguered by issues such as sensitivity to high temperature, expensive and prone to batch-to-batch variations. Aptamers are suitable alternatives to antibodies as they are cheaper and have no batch-to-batch variations compared to antibodies. In this study, DNA aptamer selection against CHIKV E2 proteins was performed using two different randomized ssDNA libraries. Chik-2 (96-mer) and Chik-3 (76-mer) were isolated from these two libraries and were identified as the potential aptamers against CHIKV E2 protein. The binding affinity of Chik-2 and Chik-3 against CHIKV E2 protein was estimated at 177.5 ± 32.69 nM and 30.01 ± 3.60 nM, respectively. A sandwich ELASA was developed, and this assay showed a detection limit of 2.17 x 103 PFU/mL. The sensitivity and specificity of the assay were 80 % and 100 %, respectively. The assay showed no cross-reactivity with dengue-positive samples, demonstrating the enormous diagnostic potential of these aptamers for the detection of CHIKV. [Display omitted] • In this study, DNA aptamer selection against CHIKV E2 proteins was performed using two different randomized ssDNA libraries. • Chik-2 (96-mer) and Chik-3 (76-mer) were successfully generated against CHIKV E2 protein. • A sandwich ELASA assay was developed, achieving sensitivity and specificity of 80 % and 100 %, respectively. [ABSTRACT FROM AUTHOR]

• The etiology of most encephalitis cases remained unknown. • Chikungunya virus was the predominant virus associated with encephalitis cases. • Chikungunya virus is a significant cause of encephalitis in Brazil. Encephalitis is a severe neurological syndrome for which herpesvirus and enteroviruses are the most common etiological agents. Arboviruses, a wildly diverse group of pathogens, are also critical epidemiological agents associated with encephalitis. In Brazil, little is known about the causative agents of encephalitis. We conducted a hospital surveillance for encephalitis between 2020 and 2022. Molecular (RT-PCR and qPCR) and serological (virus-specific IgM and viral antigens) techniques were performed in cerebrospinal fluid and serum samples obtained from study participants. In the 43 participants evaluated, the etiologic agent or the presence of IgM was detected in 16 (37.2%). Nine (20.9%) cases were positive for chikungunya virus (CHIKV), three (7.0%) for dengue virus, two (4.7%) for human adenovirus, one (2.3%) for varicella-zoster virus, and one (2.3%) for enterovirus. Whole-genome sequencing revealed that the CHIKV identified belongs to the East/Central/South African lineage. Herein, CHIKV is a common pathogen identified in encephalitis cases. Our results reinforce previous evidence that chikungunya represents a significant cause of encephalitis during CHIKV outbreaks and epidemics and add to existing information on the epidemiology of encephalitis in Brazil. [ABSTRACT FROM AUTHOR]

This study aims to describe post-chikungunya complications chronically developed cases in returning travelers from some epidemic/endemic regions, and the variables that are associated with the progression of acute or subacute cases to the chronic phase. This single-center retrospective cohort study included chikungunya fever cases treated at La Paz-Carlos III University Hospital in Madrid, Spain, April 2014 to September 2016, when the chikungunya outbreak in Latin America started through the time of its greatest impact. The analysis included 119 cases. Of these, 67.2 % were male, with a median age of 41.0 years [IQR 16.0 to 76.0] years. Only 25.6 % of the patients attended a pre-travel advice consultation. Most patients reported arthralgias, which significantly impacted their daily quality of life (86 %). The mean duration of joint symptoms was 129.4 days, with a median of 90 days [IQR 0 to 715]. Factors found to be associated with chronic arthralgia include female sex, country of infection, age at diagnosis, previous diseases, symptoms during the acute phase, pain in previously injured tendons/joints, acute phase severity, and various laboratory markers such as hemoglobin, hematocrit, total serum bilirubin, and creatinine. Progression to chronic arthralgia significantly increased the need for changes in daily activity. Furthermore, 42.6 % of patients with chronic arthralgia reported recurrence of symptoms once they felt they had disappeared. Targeted treatment regimens led to significant improvements in these patients. The results of this study underscore the need for: (1) comprehensive pre-travel advice; (2) effective management of patients in specialized units, alongside early diagnosis and treatment, to prevent trivialization of these viral infections; and (3) the development of interdisciplinary recommendations to assist physicians in treating patients and enhancing outcomes. [ABSTRACT FROM AUTHOR]

• Chikungunya virus (CHIKV) is a mosquito-borne pathogen capable of causing explosive, disruptive epidemics. • CHIKV infection causes acute febrile illness commonly associated with incapacitating polyarthalgia and myalgia and debilitating long term symptoms in many patients. • CHIKV virus-like particles (VLPs) are a promising vaccine modality. • Various genetic derivations and production systems have been used to generate CHIKV VLPs. • Nucleotide codon optimization improves production yields. • A CHIKV VLP of a single genotype is likely to generate protection against all other CHIKV genotypes. Chikungunya virus (CHIKV), an arbovirus from the Alphavirus genus, causes sporadic outbreaks and epidemics and can cause acute febrile illness accompanied by severe long-term arthralgias. Over 20 CHIKV vaccine candidates have been developed over the last two decades, utilizing a wide range of vaccine platforms, including virus-like particles (VLP). A CHIKV VLP vaccine candidate is among three candidates in late-stage clinical testing and has potentially promising data in nonclinical and clinical studies exploring safety and vaccine immunogenicity. Despite the consistency of the CHIKV VLP structure, vaccine candidates vary significantly in protein sequence identity, structural protein expression cassettes and their mode of production. Here, we explore the impact of CHIKV VLP coding sequence variation and the chosen expression platform, which affect VLP expression yields, antigenicity and overall vaccine immunogenicity. Additionally, we explore the potential of the CHIKV VLP platform to be modified to elicit protection against other pathogens. [ABSTRACT FROM AUTHOR]

Arboviruses are zoonotic RNA viruses maintained in nature in cycles that involve arthropod vectors. The arboviruses that cause disease in humans are members of the Bunyaviridae , Togaviridae , Flaviviridae , and Reoviridae families. These viral species have geographically and climatically restricted distributions due to particular ecological and vector features. The main emerging arboviruses in the Americas are dengue, zika, yellow fever (Flaviviridae), and chikungunya (Togaviridae). All of these viruses can be transmitted by the Aedes aegypti and Aedes albopictus mosquitoes. Although not commonly, these infections are associated with neurological complications, characterized mainly by hemorrhage, encephalitis, myelitis, acute disseminated encephalomyelitis, Guillain-Barré syndrome, and/or congenital malformations. This review describes the imaging features of the neurological complications of these emerging arbovirus infections. • The most important emerging arbovirus infections in the Americas are Dengue, Chikungunya, Zika and Yellow Fever. • Dengue can be complicated by hemorrhages, encephalitis, and immune-mediated syndromes, such as ADEM and Guillain Barré. • Chikungunya can be associated with encephalitis, myelitis, immune-mediated diseases and perinatal transmission. • Neurologic complications are associated with Zika virus infection, both when acquired before and after birth. • Although vaccine against Yellow fever is safe, cases of adverse neurological symptoms such as ADEM have been reported. [ABSTRACT FROM AUTHOR]

[Display omitted] • Coinhibitory receptors PD-1 and CTLA-4 are up-regulated during Acute Chikungunya. • In acute infection, CD4+ T cells produce high levels of cytokines IL-10 and IFN-γ. • CD39 and CD73 expressed by CD4+ T cells are downregulated in individuals with the persistence of symptoms. • Chronic Chikungunya is marked by the reduced density of perforin and granzyme B. • High levels of IL-10, IFN-γ, and CD39 and CD73 coexpression and diminished perforin + CD4+ T cells were found in individuals with edema during chronic Chikungunya. • Acute patients without arthralgia presented more cytolytic granules production. 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. [ABSTRACT FROM AUTHOR]

• This study investigated the duration of persistence of chikungunya-related arthralgia. • Statisticalanalysis of multiple cohorts of chikungunya patients was performed. • First estimates of the average rate of chronic chikungunya virus arthralgia resolution were calculated. • Varying rates of arthralgia resolution are associated with age and other factors. Arthralgia, persistent pain or stiffness of the joints, is the hallmark symptom of chronic chikungunya virus (CHIKV) disease. Associated with significant disability and reduced quality of life, arthralgia can persist for many months following CHIKV infection. Understanding the expected duration of arthralgia persistence is important for managing clinical expectations at the individual-level as well as for estimating long-term burdens on population health following a CHIKV epidemic. A review of cohort studies reporting the prevalence of arthralgia post-CHIKV infection over multiple time points was conducted. Generalized linear models were used to estimate the average rate of arthralgia resolution following CHIKV infection. Sixteen cohort studies matching the inclusion criteria were identified and included in the analysis. An average rate of arthralgia resolution of 10.85% (95% confidence interval (CI) 9.05–12.66%) per month was estimated across studies, corresponding to an expected median time to arthralgia resolution of 6.39 months (95% CI 5.48–7.66 months) and an expected arthralgia prevalence of 72.21% (95% CI 68.40–76.23%) at 3 months post-CHIKV infection. Estimates of the average rate of arthralgia resolution and the expected prevalence of arthralgia over time post-CHIKV infection were derived. These can help inform expectations regarding the long-term public health burdens associated with CHIKV epidemics. [ABSTRACT FROM AUTHOR]

Chikungunya (CHIKV) es un virus RNA endémico en algunas regiones de Asia y África. En Colombia en el año 2014 inicia su dispersión de manera explosiva y rápida. La presentación del CHIKV es una condición febril con síntomas musculoesqueléticos que pueden progresar a artropatía erosiva y deformidad poliarticular. El propósito de este estudio es evaluar en pacientes aquejados por la infección por CHIKV en Neiva, Huila que acuden a la consulta de Reumatología, el comportamiento sintomático y serológico, y describir comorbilidades asociadas a la fase crónica de la enfermedad. Se realizó un análisis observacional, longitudinal y retrospectivo, de datos recolectados en 410 pacientes aquejados por el virus CHIKV con síntomas de más de tres meses de duración que persistían con afecciones musculoesqueléticas y articulares. Los pacientes fueron clasificados según su compromiso en: artralgias postvirales, poliartritis postviral, artritis reumatoide (AR) postCHIKV, espondiloartritis postCHIKV y reumatismo de tejidos blandos. El análisis estadístico fue realizado usando SPSS software (versión 24). Se llevó a cabo análisis descriptivo para evaluar variables cuantitativas como la media (desviación estándar) y variables categóricas como la frecuencia (%). Las variables categóricas fueron comparadas usando la ecuación X 2 . Como significancia estadística se consideró una p < 0,05. De los 410 pacientes, 89,23% fueron mujeres, con compromiso poliarticular en 92,26% de los casos. El 49,83% de los pacientes presentaban de base osteoartritis. Al momento de la evaluación en la consulta de Reumatología, 46,3% de los pacientes cursaron con artralgias no inflamatorias persistentes y 53,7% de los casos presentaban artritis al examen físico, de los cuales, de manera remarcable 20,3% cumplieron criterios para AR postCHIKV. El desarrollo de síntomas musculoesqueléticos luego de la infección por CHIKV es un problema de salud pública bastante serio, con complicaciones persistentes y riesgo de morbilidad a largo plazo en la vida real. La presencia de artritis postviral neta es de resaltar, sin embargo, el desarrollo de AR postCHIKV requiere usualmente medidas de índole farmacológico más avanzadas, incluso, en algunos casos es necesario referir a los pacientes a terapia biológica. La presencia de síntomas de insuficiencia venosa en miembros inferiores desarrollados con la infección por CHIKV, fue un hallazgo incidental que requiere de un estudio más preciso. Chikungunya (CHIKV), is an endemic RNA virus in some regions of Asia and Africa. In Colombia in 2014, its spread starts explosively and quickly. The presentation of CHIKV is a febrile condition, with musculoskeletal symptoms, which can progress to erosive arthropathy and polyarticular deformity. The purpose of this study is to evaluate in patients suffering from CHIKV infection in Neiva, Huila who attend the Rheumatology clinic, the symptomatic and serological behavior, and to describe comorbidities associated to the chronic phase of the disease. An observational, longitudinal and retrospective analysis of data collected in 410 patients afflicted with the CHIKV virus, with symptoms lasting more than 3 months, who persisted with musculoskeletal and joint symptoms. The patients were classified according to their commitment in post-viral arthralgias, polyarthritis post viral, Rheumatoid Arthritis (RA) post CHIKV, Spondyloarthritis postCHIKV, and soft tissue rheumatism. The statistical analysis was performed using SPSS software (version 24). A descriptive analysis was carried out to evaluate quantitative variables such as the mean (standard deviation), and categorical variables such as frequency (%). The categorical variables were compared using the Chi-square equation. As a statistical significance, a p less than.05 was considered. Of the 410 patients, 89.23% were women, with polyarticular involvement in 92.26% of the cases. Of the patients, 49.83% had osteoarthritis. At the time of the evaluation in the Rheumatology clinic, 46.3% of the cases presented persistent non-inflammatory arthralgias, and 53.7% of the patients underwent arthritis on physical examination, of which, remarkably, 20.3% met the criteria for rheumatoid arthritis postCHIKV. The development of musculoskeletal symptoms after CHIKV infection is a very serious public health problem, with persistent complications and long-term morbidity risk in real life. The presence of net postviral arthritis is noteworthy, however the development of postCHIKV rheumatoid arthritis usually requires more advanced pharmacological measures, including, in some cases, transition to biological therapy. The presence of symptoms of venous insufficiency in the lower limbs that developed with CHIKV infection was an incidental finding that requires a more precise study. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to determine the seroprevalence and risk factors of chikungunya (CHIKV), dengue (DENV), and Zika (ZIKV) viruses in Tanzania. Methods: The study covered the districts of Buhigwe, Kalambo, Kilindi, Kinondoni, Kondoa, Kyela, Mvomero, and Ukerewe in Tanzania. Blood samples were collected from individuals recruited from households and healthcare facilities. An ELISA was used to screen for immunoglobulin G antibodies against CHIKV, DENV, and ZIKV. Results: A total of 1818 participants (median age 34 years) were recruited. The overall CHIKV, DENV, and ZIKV seroprevalence rates were 28.0%, 16.1%, and 6.8%, respectively. CHIKV prevalence was highest in Buhigwe (46.8%), DENV in Kinondoni (43.8%), and ZIKV in Ukerewe (10.6%) and Mvomero (10.6%). Increasing age and frequent mosquito bites were significantly associated with CHIKV and DENV seropositivity (P < 0.05). Having piped water or the presence of stagnant water around the home (P < 0.01) were associated with higher odds of DENV seropositivity. Fever was significantly associated with increased odds of CHIKV seropositivity (P < 0.001). Visiting mines had higher odds of ZIKV seropositivity (P < 0.05). Conclusions: These findings indicate that DENV, CHIKV, and ZIKV are circulating in diverse ecological zones of Tanzania. There is a need to strengthen the control of mosquito-borne viral diseases in Tanzania. [ABSTRACT FROM AUTHOR]

• A report of a Chikungunya (CHIK) outbreak in the Republic of Congo in 2019 • Malaria endemicity in Congo was also reported • There was a 14% co-infection of CHIK and malaria • IL-13 levels increased in patients with co-infection • Molecular tools provided better diagnosis of CHIK infection Accurate diagnosis of chikungunya (CHIK) is essential for effective disease management and surveillance. In a cohort of febrile Congolese patients, available diagnostic methods widely used in CHIK diagnosis were evaluated. In addition, plasma cytokines were quantified in CHIK patients and those coinfected with malaria compared with healthy controls. Between June and November 2019, a total of 107 febrile patients with suspected CHIK were subjected to differential diagnosis both for CHIK and malaria. Patients were screened for CHIK virus using molecular diagnosis by real-time PCR, serologic testing by IgM-specific and IgG-specific ELISAs, and lateral flow-based method with rapid diagnostic test (RDT), while malaria diagnosis was confirmed by PCR methods. Pro-inflammatory (IL-12, IL-16, IFN-γ, TNF-α) and anti-inflammatory (IL-4, IL-10, IL-13) cytokines were quantified in patients and healthy controls by ELISA assays. Molecular diagnoses revealed that 57% (61/107) were positive for CHIK by RT-PCR, while serologic testing revealed 31% (33/107) and 9% (10/107) seropositivity for anti- IgM and IgG, respectively. None of the patients were CHIK RDT-positive. Also, 27% (29/107) were PCR-positive for malaria. Among the malaria-positive patients, 14% (15/107) were co-infected with CHIK and 13% (14/107) were monoinfection. Plasma IL-12 and TNF-α levels were increased in patients with malaria and IL-13 levels were increased in patients with co-infection (p<0.05). Co-infection of malaria and CHIK were common in febrile Congolese patients. Real-time PCR was a better tool for detecting actual occurrences of CHIK in a malaria holoendemic area. [ABSTRACT FROM AUTHOR]

• Chikungunya virus has been actively circulating in the Horn of Africa since 2017. • A French resident in Djibouti was diagnosed with chikungunya infection in 2019. • Isolated strain belongs to the Indian lineage of the ECSA genotype. • Two mutations associated with an increased fitness in Aedes aegypti were identified. • This outbreak has the potential to spread globally through shipping routes. The chikungunya virus (CHIKV) originated from Africa and has spread worldwide. Since 2017, multiple chikungunya outbreaks have been reported in the Horn of Africa, without molecular characterization. In November 2019, an autochthonous acute chikungunya infection was diagnosed in a French patient living in Djibouti, marking the re-emergence of the virus in the country. The strain was isolated and fully sequenced. Phylogenetic analysis revealed that the Djiboutian strain belongs to the Indian lineage of the Eastern/Central/South African (ECSA) genotype. Two mutations highly increasing the virus's fitness in Aedes aegypti , the sole vector present in Djibouti city, were identified. [ABSTRACT FROM AUTHOR]

Les arboviroses représentent un problème de santé publique majeur dans les pays tropicaux et sont émergentes dans les pays tempérés. Ainsi, en France métropolitaine, des cas autochtones de dengue, de chikungunya et de Zika sont rapportés depuis quelques années dans le pourtour méditerranéen. La prévention repose principalement sur la mise en place d'un système de surveillance et sur la lutte antivectorielle. Arboviruses represent a major public health problem in tropical countries and are emerging in temperate countries. In metropolitan France, indigenous cases of dengue, chikungunya or Zika virus disease have been reported since some years in the Mediterranean region. Prevention is mainly based on the implementation of a surveillance system and on vector control. [ABSTRACT FROM AUTHOR]

The first autochthonous case and the first outbreak of chikungunya in Taiwan occurred during July-October 2019, with a total of 21 cases confirmed. Genetic analysis revealed the strains belonged to East/Central/South African genotype and had 99.95%-100% identity with the strains from the imported cases from Myanmar in 2019. This event confirmed that the imported chikungunya cases has the potential to cause autochthonous transmission in Taiwan; intensified surveillance and vector control measures are essential to contain the outbreak. [ABSTRACT FROM AUTHOR]

This study aims to determine the frequency and clinical manifestations of dengue and chikungunya viral infections in the district hospital of Mfou, Centre region of Cameroon where malaria is endemic. Blood samples were collected from suspected cases and tested for Plasmodium parasites and for the molecular detection of viral RNAs (dengue, zika and chikungunya viruses) using TRIOPLEX qPCR. A total of 108 patients were clinically suspected among which 25 % were male and 50 % were less than 15.5 years old. Of these 14.8 % (16/108) and 2.8 % (3/108) had acute dengue and chikungunya fevers respectively. Co-infection with malaria was reported in 56.3 % (9/16) of Dengue cases and 33.3 % (1/3) of chikungunya cases. Clinical profiling further revealed that nausea and vomiting show a significant difference in dengue infected individuals to those of non-infected individuals (P = 0.027). The presence of dengue fever and chikungunya fever and the absence of specific clinical manifestations highlight the need to strengthen surveillance of acute febrile infections for a better estimation of the burden of arboviruses. [ABSTRACT FROM AUTHOR]

• Anodal tDCS over M1 reduces pain in people with chronic CHIKV arthralgia. • tDCS may provide functional benefits in chronic CHIKV arthralgia. • tDCS is an easy to use and low-cost intervention that could be used for arthralgia. Chikungunya virus (CHIKV) is a globally prevalent pathogen, with outbreaks occurring in tropical regions. Chronic pain is the main symptom reported and is associated with decreased mobility and disability. Transcranial direct current stimulation (tDCS) is emerging as a new therapeutic tool for chronic arthralgia. To evaluate the effectiveness of 10 consecutive sessions of anodal tDCS on pain (primary outcome) in participants with chronic CHIKV arthralgia. Secondary outcomes included functional status, quality of life, and mood. In this randomized, double-blind, placebo-controlled trial, 30 participants with chronic CHIKV arthralgia were randomly assigned to receive either active (n = 15) or sham (n = 15) tDCS. The active group received 10 consecutive sessions of tDCS over M1 using the C3/Fp2 montage (2 mA for 20 min). Visual analog scale of pain (VAS), health assessment questionnaire (HAQ), short-form 36 health survey (SF-36), pain catastrophizing scale, Hamilton anxiety scale (HAS), timed up and go (TUG) test, lumbar dynamometry, 30-s arm curl and 2-min step test were assessed at baseline, day 10 and at 2 follow-up visits. There was a significant interaction between group and time on pain (p = 0.03; effect size 95 % CI 0.9 (-1.67 to -0.16), with a significant time interaction (p = 0.0001). There was no interaction between time and group for the 2-minute step test (p = 0.18), but the groups differed significantly at day 10 (p = 0.01), first follow-up (p = 0.01) and second follow-up (p = 0.03). HAQ and SF-36 improved but not significantly. There was no significant improvement in mental health, and physical tests. tDCS appears to be a promising intervention for reducing pain in participants with chronic CHIKV arthralgia, although further research is needed to confirm these findings and explore potential long-term benefits. Brazilian Registry of Clinical Trials (ReBEC): RBR-245rh7. [ABSTRACT FROM AUTHOR]

Chikungunya fever is an arboviral illness caused by chikungunya virus (CHIKV) and transmitted by the bite of Aedes aegypti and Aedes albopictus. It is an RNA virus belonging to the genus Alphavirus and family Togaviridae. We present a case series of three patients with chikungunya illness developing para/post-infectious myeloradiculoneuropathy.These patients developed neurological symptoms in the form of bilateral lower limb weakness with sensory and bowel involvement after the recovery from the initial acute episode of chikungunya fever. Clinical examination findings suggested myeloradiculoneuropathy with normal Magnetic Resonance Imaging of the Spine, with the nerve conduction study showing sensorimotor axonal polyneuropathy. All the patients were treated with 1 g of methylprednisolone once a day for five days, and case 2 was given intravenous immunoglobulin also. In the follow-up, cases 1 and 2 showed complete recovery without recurrence, and case 3 did not show improvement at one month. [ABSTRACT FROM AUTHOR]

Chikungunya virus (CHIKV) is a single positive-stranded RNA virus of the Togaviridae family and Alphavirus genus, with a typical lipid bilayer envelope structure, and is the causative agent of human chikungunya fever (CHIKF). The U.S. Food and Drug Administration has recently approved the first chikungunya vaccine, Ixchiq; however, vaccination rates are low, and CHIKF is prevalent owing to its periodic outbreaks. Thus, developing effective anti-CHIKV drugs in clinical settings is imperative. Viral proteins encoded by the CHIKV genome play vital roles in all stages of infection, and developing therapeutic agents that target these CHIKV proteins is an effective strategy to improve CHIKF treatment efficacy and reduce mortality rates. Therefore, in the present review article, we aimed to investigate the basic structure, function, and replication cycle of CHIKV and comprehensively outline the current status and future advancements in anti-CHIKV drug development, specifically targeting nonstructural (ns) proteins, including nsP1, nsP2, nsP3, and nsP4 and structural proteins such as capsid (C), E3, E2, 6K, and E1. [ABSTRACT FROM AUTHOR]

Mosquito-borne viruses, or arboviruses, have been part of the infectious disease landscape for centuries, and are often, but not exclusively, endemic to equatorial and subtropical regions of the world. The past two decades saw the re-emergence of arthritogenic alphaviruses, a genus of arboviruses that includes several members that cause severe arthritic disease. Recent outbreaks further highlight the substantial public health burden caused by these viruses. Arthritogenic alphaviruses are often reported in the context of focused outbreaks in specific regions (eg, Caribbean, southeast Asia, and Indian Ocean) and cause debilitating acute disease that can extend to chronic manifestations for years after infection. These viruses are classified among several antigenic complexes, span a range of hosts and mosquito vectors, and can be distributed along specific geographical locations. In this Review, we highlight key features of alphaviruses that are known to cause arthritic disease in humans and outline the present findings pertaining to classification, immunogenicity, pathogenesis, and experimental approaches aimed at limiting disease manifestations. Although the most prominent alphavirus outbreaks in the past 15 years featured chikungunya virus, and a large body of work has been dedicated to understanding chikungunya disease mechanisms, this Review will instead focus on other arthritogenic alphaviruses that have been identified globally and provide a comprehensive appraisal of present and future research directions. [ABSTRACT FROM AUTHOR]

Controlling diseases such as dengue fever, chikungunya and zika fever by introduction of the intracellular parasitic bacterium Wolbachia in mosquito populations which are their vectors, is presently quite a promising tool to reduce their spread. While description of the conditions of such experiments has received ample attention from biologists, entomologists and applied mathematicians, the issue of effective scheduling of the releases remains an interesting problem. Having in mind the important uncertainties present in the dynamics of the two populations in interaction, we attempt here to identify general ideas for building feedback-based release strategies, enforceable to a variety of models and situations. These principles are exemplified by several feedback control laws whose stabilizing properties are demonstrated, illustrated numerically and compared, when applied to a model retrieved from [P.-A. Bliman et al., Ensuring successful introduction of Wolbachia in natural populations of Aedes aegypti by means of feedback control. J. of Math. Bio. 76(5):1269–1300, 2018]. The contribution is believed to be also of potential interest to tackle other important issues related to the biological control of vectors and pests. A crucial use of the theory of monotone dynamical systems is made in the derivations. [ABSTRACT FROM AUTHOR]

The Northeast region of Brazil registered the second-highest incidence proportion of Chikungunya fever in 2019. In that year, an outbreak consisting of patients presenting with febrile disease associated with joint pain was reported by the public primary health care service in the city of Natal, in the state of Rio Grande do Norte, in March 2019. At first, the aetiological agent of the disease was undetermined. Since much is still unknown about chikungunya virus' (CHIKV) genomic diversity and evolutionary history in this northeasternmost state, we used a combination of portable whole-genome sequencing, molecular clock, and epidemiological analyses that revealed the reintroduction of the CHIKV East-Central-South-African (ECSA) lineage into Rio Grande do Norte. We estimated that the CHIKV ECSA lineage was first introduced into Rio Grande do Norte in early June 2014, while the 2019 outbreak clade diverged around April 2018, during a period of increased Chikungunya incidence in the Southeast region, which might have acted as a source of virus dispersion towards the Northeast region. Together, these results confirm that the ECSA lineage continues to spread across the country through interregional importation events, likely mediated by human mobility. [ABSTRACT FROM AUTHOR]

The primary aim of this study was to evaluate the temporal correlation between Wikitrends and conventional surveillance data generated for Chikungunya, Dengue, Zika, and West Nile Virus infection reported by bulletin of Italian National Institute of Health (Istituto Superiore di Sanità in italian, ISS). A cross-sectional study design was used. The reported cases of Dengue and Chikungunya were selected from July 2015 to December 2019. For West Nile Virus, the bulletins are issued in the period June–November (6 months) of the years 2015–2019, and for Zika virus, the data reported in the ISS bulletin start from January 2016. From Wikipedia Trends, we extracted the number of monthly views by users from the July 2015 to December 2019 of the pages Chikungunya, Dengue, Zika virus, and West Nile Virus. A correlation was observed between the bulletin of ISS and Wikipedia Wikitrends, the correlation was strong for Chikungunya and West Nile Virus (r = 0.9605; r = 0.9556, respectively), and highly statistically significant with P -values <0.001. The correlation was moderate for Dengue and Zika virus (r = 0.6053; r = 0.5888, respectively), but highly statistically significant with P -values <0.001. Classical surveillance system should be integrated with the tools of digital epidemiology that have potential role in public health for the dynamic information and provide near real-time indicators of the spread of infectious disease. • The temporal correlation between Chikungunya and West Nile Virus reported cases and Wikipedia's search trends was strong. • The temporal correlation between Dengue and Zika Virus cases and Wikipedia's search trends was moderate but highly significant. • The novel surveillance systems should be used more and in combination with traditional systems. [ABSTRACT FROM AUTHOR]

• It develops an optimization procedure on a new rainfall dependent nonlinear dynamic population model. • The model finds solutions that contribute to reduce the vector infestation and minimize both the social and economic costs. • Numerical simulations consider the case for the city of Lavras, Minas Gerais State, Brazil, during the spring and summer. • The findings indicate policy solutions with a low total cost and a higher efficiency, reflecting the decline in vector populations. According to the World Health Organization, more than 80% of the world's population lives in areas at risk of vector-borne diseases transmission. The Aedes aegypti mosquito is through its bite the responsible vector for transmitting many diseases, such as dengue, Zika, and chikungunya fever, with 50–100 million estimated cases of dengue fever yearly worldwide. The vector control is the recommended action to mitigate the transmission, but public health organizations face limitations on budget, mainly in emerging countries. In that sense, the efficiency in vector control with fewer costs becomes reasonably desirable. The present work aims to develop an optimization procedure on a new rainfall dependent nonlinear dynamic population model, which is adjusted by the data obtained from females captured in traps. Thus, we can find solutions that contribute to reduce the vector infestation and minimize both the social and economic costs involved. The problem is approached over two different strategies: simultaneous step size control (SSC) and simultaneous descending control (SDC). Control strategies may vary according to the type of control, the time, and the application period throughout the year. Numerical simulations consider the case for the city of Lavras, Minas Gerais State, Brazil, during the spring and summer. The Real-Biased Genetic Algorithm was used in a mono-objective optimization problem to find optimal intervention solutions. The findings indicate policy solutions with a low total cost and a high efficiency, reflecting the decline in vector populations according to the weather. [ABSTRACT FROM AUTHOR]

Ras-GTPase activating protein SH3-domain-binding proteins (G3BP) are a small family of RNA-binding proteins implicated in regulating gene expression. Changes in expression of G3BPs are correlated to several cancers including thyroid, colon, pancreatic and breast cancer. G3BPs are important regulators of stress granule (SG) formation and function. SG are ribonucleoprotein (RNP) particles that respond to cellular stresses to triage mRNA resulting in transcripts being selectively degraded, stored or translated resulting in a change of gene expression which confers a survival response to the cell. These changes in gene expression contribute to the development of drug resistance. Many RNA viruses, including Chikungunya (and potentially Coronavirus), dismantle SG so that the cell cannot respond to the viral infection. Non-structural protein 3 (nsP3), from the Chikungunya virus, has been shown to translocate G3BP away from SG. Interestingly in cancer cells, the formation of SG is correlated to drug-resistance and blocking SG formation has been shown to reestablish the efficacy of the anticancer drug bortezomib. Chikungunya nsP3 was transfected into breast cancer cell lines T47D and MCF7 to disrupt SG formation. Changes in the cytotoxicity of bortezomib were measured. Bortezomib cytotoxicity in breast cancer cell lines changed with a 22 fold decrease in its IC 50 for T47D and a 7 fold decrease for MCF7 cells. Chikungunya nsP3 disrupts SG formation. As a result, it increases the cytotoxicity of the FDA approved drug, bortezomib. In addition, the increased cytotoxicity appears to correlate to improved bortezomib selectivity when compared to control cell lines. [ABSTRACT FROM AUTHOR]

Dengue fever, Chikungunya fever, and Zika virus infection have similar symptoms and overlapping areas of endemicity and so cannot be distinguished clinically. Rapid diagnosis tests are available for each infection but each test covers only single target. There are PCR-based methods available that test for all three infections simultaneously, not applicable for in-vitro diagnostic use. The aim of this study was to evaluate the diagnostic accuracy of a new point-of-care testing (LAMP POCT) based on loop-mediated isothermal amplification method that tests for all three viruses simultaneously, using serum or urine samples, and takes about 45 min. LAMP POCT was evaluated as the comparator on 67 individuals, of whom 56 had dengue, three had Chikungunya, two had Zika virus infection and six did not have any kind of these infections confirmed by RT-PCR. Among individuals with dengue, the sensitivity of LAMP POCT was 100% in samples collected in the first 3 days after illness onset, all three patients with Chikungunya were LAMP POCT positive, and both patients with Zika virus infection were LAMP POCT negative. There were no false-positive test results. LAMP POCT has potential utility as a point-of-care combination test for dengue and Chikungunya viruses, but further prospective studies are needed among individuals with Chikungunya virus and Zika virus infection, using serum and urine samples. [ABSTRACT FROM AUTHOR]

Background: Since 2015, the arthropod-borne viruses (arboviruses) Zika and chikungunya have spread across the Americas causing outbreaks, accompanied by increases in immune-mediated and infectious neurological disease. The spectrum of neurological manifestations linked to these viruses, and the importance of dual infection, are not known fully. We aimed to investigate whether neurological presentations differed according to the infecting arbovirus, and whether patients with dual infection had a different disease spectrum or severity.Methods: We report a prospective observational study done during epidemics of Zika and chikungunya viruses in Recife, Pernambuco, a dengue-endemic area of Brazil. We recruited adults aged 18 years or older referred to Hospital da Restauração, a secondary-level and tertiary-level hospital, with suspected acute neurological disease and a history of suspected arboviral infection. We looked for evidence of Zika, chikungunya, or dengue infection by viral RNA or specific IgM antibodies in serum or CSF. We grouped patients according to their arbovirus laboratory diagnosis and then compared demographic and clinical characteristics.Findings: Between Dec 4, 2014, and Dec 4, 2016, 1410 patients were admitted to the hospital neurology service; 201 (14%) had symptoms consistent with arbovirus infection and sufficient samples for diagnostic testing and were included in the study. The median age was 48 years (IQR 34-60), and 106 (53%) were women. 148 (74%) of 201 patients had laboratory evidence of arboviral infection. 98 (49%) of them had a single viral infection (41 [20%] had Zika, 55 [27%] had chikungunya, and two [1%] had dengue infection), whereas 50 (25%) had evidence of dual infection, mostly with Zika and chikungunya viruses (46 [23%] patients). Patients positive for arbovirus infection presented with a broad range of CNS and peripheral nervous system (PNS) disease. Chikungunya infection was more often associated with CNS disease (26 [47%] of 55 patients with chikungunya infection vs six [15%] of 41 with Zika infection; p=0·0008), especially myelitis (12 [22%] patients). Zika infection was more often associated with PNS disease (26 [63%] of 41 patients with Zika infection vs nine [16%] of 55 with chikungunya infection; p≤0·0001), particularly Guillain-Barré syndrome (25 [61%] patients). Patients with Guillain-Barré syndrome who had Zika and chikungunya dual infection had more aggressive disease, requiring intensive care support and longer hospital stays, than those with mono-infection (median 24 days [IQR 20-30] vs 17 days [10-20]; p=0·0028). Eight (17%) of 46 patients with Zika and chikungunya dual infection had a stroke or transient ischaemic attack, compared with five (6%) of 96 patients with Zika or chikungunya mono-infection (p=0·047).Interpretation: There is a wide and overlapping spectrum of neurological manifestations caused by Zika or chikungunya mono-infection and by dual infections. The possible increased risk of acute cerebrovascular disease in patients with dual infection merits further investigation.Funding: Fundação do Amparo a Ciência e Tecnologia de Pernambuco (FACEPE), EU's Horizon 2020 research and innovation programme, National Institute for Health Research.Translations: For the Portuguese and Spanish translations of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]