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Introduction: Chikungunya Fever is an arbovirus transmitted by Aedes aegypti or Aedes albopictus mosquitoes. Neurological manifestations associated with arboviruses such as Dengue and Zika Virus were reported between 2017 and 2019., Aim: To describe the impact of physical therapy management on pain, mobility, and strength for a patient with transverse myelitis seropositive to Chikungunya., Methods: A 29-year-old patient with transverse myelitis due to Chikungunya virus infection was subjected to physiotherapeutic evaluation and intervention for the management of pain, mobility, and lower limb strength. Pain intensity, tactile sensitivity for light touch and pain, and thermal sensitivity were assessed by the Numeric Pain Rating Scale (NPRS), aesthesiometer and pin-prick stimulator, and hot/cold test tubes, respectively. Functional mobility and lower limbs strength were assessed by the Timed Up and Go (TUG) test and the 30-s Chair-Stand test (30 CST), respectively. The physiotherapeutic protocol included kinesiotherapy, Transcutaneous Electrical Nerve Stimulation, and Functional Electrical Stimulation., Results: After 20 sessions of a multimodal physical therapy intervention, all joints tested by NPRS showed pain reduction: lumbar spine (57.15%), hip and ankles (100%), right knee (28.58%), and left knee (33.34%).There was an improvement in performing the TUG test at "getting up" and "sitting down" phases (decrease of 30% and 23%, respectively), while the number of repetitions in the 30 TFC increased by 75%, in addition, there was an improvement in performance in the tests, with more autonomy and independence., Conclusion: At the end of the physiotherapeutic intervention, pain, mobility, and strength of the lower limbs were improved., Competing Interests: Declaration of competing interest All authors have approved the manuscript and have no conflicts of interest to declarate., (Copyright © 2024. Published by Elsevier Ltd.)

RNA interference (RNAi) is a process in which small RNA molecules (such as small interfering RNAs or siRNAs) bind to specific messenger RNAs (mRNAs), leading to its degradation and inhibition of protein synthesis. Our studies have shown that RNAi can effectively silence genes involved in the replication of the Chikungunya virus (CHIKV) in cells. However, these investigations were performed only in laboratory settings and have yet to be tested in human clinical trials. Researchers need to conduct more research to determine the safety and efficacy of RNAi-based therapies as a therapeutic agent to treat viral infections. In this review, the history of evolution of siRNA as an inhibitor of protein synthesis, along with its current developments, is discussed based on our experience. Moreover, this review examines the hurdles and future implications associated with siRNA based therapeutic approaches.

Chikungunya virus, an arthropod-borne pathogen is recognized by the World Health Organization as a top priority Emerging Infectious Disease and is ranked fourth in public health needs according to the Coalition for Epidemic Preparedness Innovations. Despite its substantial impact, as evidenced by an annual estimate of 120 274 disability-adjusted life years, our understanding of the chronic aspects of chikungunya disease remains limited. This review focuses on chronic chikungunya disease, emphasizing its clinical manifestations, immunopathogenesis, therapeutic options and disease burden., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Association of Physicians.)

Background: 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., Objective: 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., Methods: 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., Results: 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., Conclusion: 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., Trial Registration: Brazilian Registry of Clinical Trials (ReBEC): RBR-245rh7., Competing Interests: Declaration of competing interest The City University of New York has a patent on brain stimulation with MB as the inventor. MB has equity in Soterix Medical Inc. No conflict of interest was declared by the other authors., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

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., (© 2023. The Author(s).)

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., (© 2023. The Author(s).)

The chikungunya virus is an arthritogenic alphavirus. Acute infection may be followed by persistent arthralgia, often causing significant functional impairment. The 2014-2015 chikungunya fever (CHIKF) epidemic resulted in a marked increase in cases presenting to rheumatology and tropical diseases services. A combined multidisciplinary rheumatology-tropical diseases service for assessment, management, and follow-up of patients with proven CHIKF and persistent (≥ 4 weeks) arthralgia was proposed and rapidly developed at The Hospital for Tropical Diseases in London. Rapid set up of a multidisciplinary clinic in response to the epidemic was achieved. Of a total of 54 patients, 21 (38.9%) patients with CHIKF developed persistent arthralgia and were reviewed by the multidisciplinary service. A combined assessment approach enabled comprehensive multidisciplinary assessment of CHIKF, assessment of joint pathology through ultrasound, and appropriate follow-up. A combined rheumatology-tropical diseases service was successfully used to identify and assess CHIKF-associated morbidity. Future outbreaks may be approached by establishing tailored multidisciplinary clinics.

Introduction: The chikungunya virus infection is still an epidemic in Brazil with an incidence of 59.4 cases per 100 000 in the Northeast region. More than 60% of the patients present relapsing and remitting chronic arthralgia with debilitating pain lasting for years. Transcranial direct current stimulation (tDCS) appears promising as a novel neuromodulation approach for pain-related networks to alleviate pain in several pain syndromes. Our objective is to evaluate the effectiveness of tDCS (C3/Fp2 montage) on pain, muscle strength, functionality and quality of life in chronic arthralgia., Methods and Analysis: This protocol is a single-centre, parallel-design, double-blind, randomised, sham-controlled trial. Forty participants will be randomised to either an active or sham tDCS. A total of 10 sessions will be administered over 2 weeks (one per weekday) using a monophasic continuous current with an intensity of 2 mA for 20 min. Participants will be evaluated at baseline, after the 10th session, 2 weeks and 4 weeks after intervention., Primary Outcome: pain assessed using numeric rating scale and algometry., Secondary Outcomes: muscle strength, functionality and quality of life. The effects of stimulation will be calculated using a mixed analysis of variance model., Ethics and Dissemination: The study was approved by the ethics committee of the Faculty of Health Sciences of Trairí, Federal University of Rio Grande do Norte (No. 2.413.851) and registered on the Brazilian Registry of Clinical Trials. Study results will be disseminated through presentations at conferences and publications in peer-reviewed journals., Trial Registration Number: RBR-469yd6., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Post-chikungunya joint pain (arthritis or arthralgia) is a clinical concern in endemic regions as it may cause a debilitating illness sometimes years after the acute infection. This systematic review analyses evidence from controlled clinical trials regarding the efficacy of pharmacological and non-pharmacological interventions to treat post-chikungunya joint pain. PubMed, EMBASE, Scopus, Cochrane library and Web of Science were searched for eligible studies without any language or time limits, excluding retrospective studies, and prospective observational studies without a control group. Eleven studies met the inclusion criteria. Seven assessed pharmacological interventions and four assessed non-pharmacological interventions (exercise, neuromodulation). The number of participants in each intervention arm varied from 10 to 75 and, given the heterogeneity of interventions, a meta-analysis was not possible. Available evidence does not show any added benefit of chloroquine, hydroxychloroquine, stand-alone methotrexate or ribavirin compared with anti-inflammatory drugs or placebo/no treatment. Non-steroidal anti-inflammatory drugs may reduce pain up to 24 wk of treatment but long-term residual impact after stopping treatment is unassessed. Currently, there is also no high certainty evidence to recommend non-pharmacological methods such as exercise and neuromodulation., (© The Author(s) 2022. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Arboviral infections such as Chikungunya (CHIKV), Dengue (DENV) and Zika (ZIKV) are a major disease burden in tropical and sub-tropical countries, and there are no effective vaccinations or therapeutic drugs available at this time. Understanding the role of the T cell response is very important when designing effective vaccines. Currently, comprehensive identification of T cell epitopes during a DENV infection shows that CD8 and CD4 T cells and their specific phenotypes play protective and pathogenic roles. The protective role of CD8 T cells in DENV is carried out through the killing of infected cells and the production of proinflammatory cytokines, as CD4 T cells enhance B cell and CD8 T cell activities. A limited number of studies attempted to identify the involvement of T cells in CHIKV and ZIKV infection. The identification of human immunodominant ZIKV viral epitopes responsive to specific T cells is scarce, and none have been identified for CHIKV. In CHIKV infection, CD8 T cells are activated during the acute phase in the lymph nodes/blood, and CD4 T cells are activated during the chronic phase in the joints/muscles. Studies on the role of T cells in ZIKV-neuropathogenesis are limited and need to be explored. Many studies have shown the modulating actions of T cells due to cross-reactivity between DENV-ZIKV co-infections and have repeated heterologous/homologous DENV infection, which is an important factor to consider when developing an effective vaccine.

Chikungunya is caused by CHIKV (chikungunya virus), an emerging and re-emerging arthropod-vectored viral infection that causes a febrile disease with primarily long term sequelae of arthralgia and myalgia and is fatal in a small fraction of infected patients. Sporadic outbreaks have been reported from different parts of the world chiefly Africa, Asia, the Indian and Pacific ocean regions, Europe and lately even in the Americas. Currently, treatment is primarily symptomatic as no vaccine, antibody-mediated immunotherapy or antivirals are available. Chikungunya belongs to a family of arthritogenic alphaviruses which have many pathophysiological similarities. Chikungunya arthritis has similarities and differences with rheumatoid arthritis. Although research into arthritis caused by these alphaviruses have been ongoing for decades and significant progress has been made, the mechanisms underlying viral infection and arthritis are not well understood. In this review, we give a background to chikungunya and the causative virus, outline the history of alphavirus arthritis research and then give an overview of findings on arthritis caused by CHIKV. We also discuss treatment options and the research done so far on various therapeutic intervention strategies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Chikungunya virus (CHIKV) is responsible for a self-limited illness that can evolve into long-lasting painful joint inflammation. In this study, we report a novel experimental CHIKV vaccine formulation of lipid nanoparticles loaded with a recombinant protein derived from the E2 structural protein. This antigen fragment, designated ∆E2.1, maintained the antigenicity of the native viral protein and was specifically recognized by antibodies induced in CHIKV-infected patients. The antigen has been formulated into nanoparticles consisting of nano-multilamellar vesicles (NMVs) combined with the adjuvant monophosphoryl lipid A (MPLA). The vaccine formulation demonstrated a depot effect, leading to controlled antigen release, and induced strong antibody responses significantly higher than in mice immunized with the purified protein combined with the adjuvant. More relevantly, E2-specific antibodies raised in mice immunized with ∆E2.1-loaded NMV-MPLA neutralized CHIKV under in vitro conditions. Taken together, the results demonstrated that the new nanoparticle-based vaccine formulation represents a promising approach for the development of effective anti-CHIKV vaccines., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The role of the emergency provider lies at the forefront of recognition and treatment of novel and re-emerging infectious diseases in children. Familiarity with disease presentations that might be considered rare, such as vaccine-preventable and non-endemic illnesses, is essential in identifying and controlling outbreaks. As we have seen thus far in the novel coronavirus pandemic, susceptibility, severity, transmission, and disease presentation can all have unique patterns in children. Emergency providers also have the potential to play a public health role by using lessons learned from the phenomena of vaccine hesitancy and refusal., Competing Interests: Disclosure C.C. Chen has no commercial or financial conflicts of interest. A. Whitehead has no commercial or financial conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The co-circulation of types of arbovirus in areas where they are endemic increased the risk of outbreaks and limited the diagnostic methods available. Here, we analyze the epidemiological profile of DENV, CHIKV and ZIKV at the serological and molecular level in patients with suspected infection with these arboviruses in the city of Juazeiro do Norte, Ceará, Brazil., Methods: In 2016, the Central Public Health Laboratory (LACEN) of Juazeiro do Norte received 182 plasma samples from patients who visited health facilities with symptoms compatible with arbovirus infection. The LACEN performed serological tests for detection of IgM/IgG to DENV and CHIKV. They then sent these samples to the Retrovirology Laboratory of the Federal University of São Paulo and Faculty of Medical of the ABC where molecular analyses to confirm the infection by DENV, ZIKV and CHIKV were performed. The prevalence of IgM/IgG antibodies and of infections confirmed by RT-qPCR were presented with 95% confidence interval., Results: In serologic analysis, 125 samples were positive for antibodies against CHIKV and all were positive for antibodies against DENV. A higher prevalence of IgG against CHIKV (63.20% with 95% CI: 45.76-70.56) than against DENV (95.05% with 95% CI: 78.09-98.12) was observed. When the samples were submitted to analysis by RT-qPCR, we observed the following prevalence: mono-infection by ZIKV of 19.23% (95% CI: 14.29-34.82) patients, mono-infection by CHIKV of 3.84% (95% CI: 2.01-5.44) and co-infection with ZIKV and CHIKV of 1.09% (95% CI: 0.89-4.56)., Conclusion: The serologic and molecular tests performed in this study were effective in analyzing the epidemiological profile of DENV, CHIKV and ZIKV in patients with suspected infection by these arboviruses in the city of Juazeiro do Norte, Ceará/Brazil., (© 2021. The Author(s).)

Reports on tropical infections among kidney transplant (KT) recipients have increased in recent years, mainly because of the growing number of KT programs located in tropical and subtropical areas, and greater mobility or migration between different areas of the world. Endemic in emerging and developing regions, like most countries in Latin America, tropical infections are an important cause of morbidity and mortality in this population. Tropical infections in KT recipients may exhibit different pathways for acquisition compared with those in nonrecipients, such as transmission through a graft and reactivation of a latent infection triggered by immunosuppression. Clinical presentation may differ compared with that in immunocompetent patients, and there are also particularities in diagnostic aspects, treatment, and prognosis. KT patients must be screened for latent infections and immunized properly. Last, drug-drug interactions between immunosuppressive agents and drugs used to treat tropical infections are an additional challenge in KT patients. In this review, we summarize the management of tropical infections in KT patients.

Context: Thousands of people worldwide have been infected by the chikungunya virus (CHIKV), and the persistence of joint pain symptoms has been considered the main problem. Neuromodulation techniques such as transcranial direct current stimulation (tDCS) act on brain areas involved in the processing of chronic pain. It was previously demonstrated that tDCS for five consecutive days significantly reduced pain in the chronic phase of chikungunya (CHIK)., Objective: To analyze the effect of alternate tDCS sessions on pain and functional capacity in individuals affected by CHIK., Methods: In a randomized clinical trial, 58 women in the chronic phase of CHIK were divided into two groups: active-tDCS (M1-S0, 2 mA, 20 min) and sham-tDCS. The Visual Analogue Scale (VAS) and the Brief Pain Inventory (BPI) were used to assess pain, while the Health Assessment Questionnaire (HAQ) assessed functional capacity. These scales were used before and after six sessions of tDCS in nonconsecutive days on the primary motor cortex, and at follow-up consultation 7 and 15 days after the last session. A repeated measures mixed-model ANOVA was used for comparison between groups (significant p-values < 0.05)., Results: A significant pain reduction (Z [3, 171] = 14.303; p < 0.0001) was observed in the tDCS group compared to the sham group; no significant difference in functional capacity was observed (Z [1.57] = 2.797; p = 0.1)., Conclusion: Our results suggest that six nonconsecutive sessions of active tDCS on M1 reduce pain in chronic CHIKV arthralgia., Competing Interests: Declaration of competing interest The City University of New York (CUNY) has IP on neuro-stimulation system and methods with author MB as inventor. MB has equity in Soterix Medical. MB serves on Boston Scientific and GlaxoSmithKline Inc. advisory boards., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Chikungunya virus (CHIKV) is a mosquito-borne pathogen that is responsible for numerous large and geographical epidemics, causing millions of cases. However, there is no vaccine or therapeutics against CHIKV infection available. Interferon-alpha (IFN-α) has been shown to produce potent antiviral responses during viral infection. Herein we demonstrated the use of an adenovirus-vectored expressed mouse IFN-α (mDEF201) as a prophylactic and therapeutic treatment against CHIKV in vivo. 6-day-old BALB/c mice were pre- or post-treated intranasally with single dose of mDEF201 at 5 x 106 PFU per mouse and challenged with lethal dose of CHIKV. Complete survival protection was observed in mice upon a single dose of mDEF201 administration 1 days prior to virus challenge. Viral load in the serum and multiple organs were significantly reduced upon mDEF201 administration in a dose dependent manner as compare with adenovirus 5 vector placebo set. Histological analysis of the mice tissue revealed that mDEF201 could significantly reduce the tissue morphological abnormities, mainly infiltration of immune cells and muscle fibre necrosis caused by CHIKV infection. In addition, administration of mDEF201 at 6 hours post CHIKV challenge also showed promising inhibitory effect against viral replication and dissemination. In conclusion, single-dose of intranasal administration with mDEF201 as a prophylactic or therapeutic agent within 6 hours post CHIKV infection is highly protective against a lethal challenge of CHIKV in the murine model., Competing Interests: The authors have declared that no competing interests exist.

Chikungunya virus (CHIKV), a mosquito-transmitted disease that belongs to the genus Alphaviruses, has been emerged as an epidemic threat over the last two decades, and the recent co-emergence of this virus along with other circulating arboviruses and comorbidities has influenced atypical mortality rate up to 10%. Genetic variation in the virus has resulted in its adaptability towards the new vector Aedes albopictus other than Aedes aegypti, which has widen the horizon of distribution towards non-tropical and non-endemic areas. As of now, no licensed vaccines or therapies are available against CHIKV; the treatment regimens for CHIKV are mostly symptomatic, based on the clinical manifestations. Development of small molecule drugs and neutralizing antibodies are potential alternatives of worth investigating until an efficient or safe vaccine is approved. Neutralizing antibodies play an important role in antiviral immunity, and their presence is a hallmark of viral infection. In this review, we describe prospects for effective vaccines and highlight importance of neutralizing antibody-based therapeutic and prophylactic applications to combat CHIKV infections. We further discuss about the progress made towards CHIKV therapeutic interventions as well as challenges and limitation associated with the vaccine development. Furthermore this review describes the lesson learned from chikungunya natural infection, which could help in better understanding for future development of antibody-based therapeutic measures.

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus, and its infection can cause long-term debilitating arthritis in humans. Currently, there are no licensed vaccines or therapeutics for human use to combat CHIKV infections. In this study, we explored the feasibility of using an anti-CHIKV monoclonal antibody (mAb) produced in wild-type (WT) and glycoengineered (∆XFT) Nicotiana benthamiana plants in treating CHIKV infection in a mouse model. CHIKV mAb was efficiently expressed and assembled in plant leaves and enriched to homogeneity by a simple purification scheme. While mAb produced in ∆XFT carried a single N-glycan species at the Fc domain, namely GnGn structures, WT produced mAb exhibited a mixture of N-glycans including the typical plant GnGnXF 3 glycans, accompanied by incompletely processed and oligomannosidic structures. Both WT and ∆XFT plant-produced mAbs demonstrated potent in vitro neutralization activity against CHIKV. Notably, both mAb glycoforms showed in vivo efficacy in a mouse model, with a slight increased efficacy by the ∆XFT-produced mAbs. This is the first report of the efficacy of plant-produced mAbs against CHIKV, which demonstrates the ability of using plants as an effective platform for production of functionally active CHIKV mAbs and implies optimization of in vivo activity by controlling Fc glycosylation., (© 2019 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Since the emergence of the chikungunya virus in Brazil in 2014, more than 700,000 cases have been reported throughout the country, corresponding to one-third of all cases reported in the Americas. In addition to its high attack rates, resulting in hundreds of thousands of cases, the disease has high chronicity rates with persistent joint manifestations for more than 3 months, which can spread to more than half of the patients affected in the acute phase. Pain associated with musculoskeletal manifestations, often disabling, has an effect on patients' quality of life at different stages of the disease. Currently, the challenge faced by specialists is identifying the best therapy to be instituted for symptom relief despite the limited number of published intervention studies. In 2016, a multidisciplinary group published pharmacological treatment protocols for pain in patients with chikungunya, which was incorporated into the guidelines for clinical management of the Brazilian Ministry of Health in 2017; in that same year, a consensus was published by the Brazilian Society of Rheumatology about diagnosis and treatment. After 5 years of experience with chikungunya epidemics, in 2019, specialists involved in the protocols of the Brazilian Society of Rheumatology and Brazilian Ministry of Health prepared an update with the main objective of developing flowcharts for the therapeutic approach of musculoskeletal manifestations in adult patients to enable specialists at different levels of healthcare to spread and apply this guideline in a systematic and simplified manner.

In 2004, a global spread of Chikungunya fever affected most tropical and subtropical regions of the world. In 2016, an outbreak occurred in Northeast Brazil with hundreds of cases documented. Solid organ transplant recipients have a modified immune response to infection and the clinical course is usually different from immunocompetent patients. The diagnosis can be challenging in this population. Most reports describe patients residing in endemic areas, although we must emphasize the importance of differential diagnosis in kidney transplanted travelers who visit endemic regions, such as Northeast Brazil. Here, we reported a case of a kidney transplant recipient that acquired Chikungunya fever after a trip to an endemic region at Northeast Brazil during the outbreak in 2016, with a good clinical evolution. We also present warning recommendations for travelers to endemic areas as additional measures to prevent disease outbreaks.

Background: We aimed to describe the clinical and laboratory features of Chikungunya disease in infants aged from 1 month to 2years., Methods: This epidemiologic study was carried out at the Pointe-à-Pitre University Hospital from May to September 2014. We collected data prospectively from infants hospitalized for Chikungunya disease., Results: A total of 154 infants were included. Hyperthermia was greater than 38.5°C the first 48h and during on average 2.7 days. Pain (on mobilization and/or cutaneous hyperesthesia and/or arthralgia) was present in 82% of the cases. Loss of appetite was reported for 62% of the infants. Initial maculopapular erythematous eruption occurred in 69% of the cases. A vesiculobullous eruption was secondarily observed in 7% of the cases. Edema on the feet and/or hands was present in 48% of the cases. Febrile seizure was observed in 12% of the cases. Lymphopenia was the most frequent laboratory finding, present in 94% of the infants. No cases of thrombocytopenia were observed. The reported complications were: bullous epidermolysis, state of epilepticus, and severe acute hepatitis., Conclusion: This study highlights a suggestive clinical presentation of Chikungunya diseases combining pain, fever, tachycardia, foot and/or hand edema. Lymphopenia, monocytosis, and the absence of thrombocytopenia were relevant biological signs., (Copyright © 2019 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Objective: Chikungunya (CHIKV) is an arbovirus that causes acute, debilitating polyarthritis. Its diagnosis can be difficult for clinicians not used to managing joint diseases or detecting synovitis. Joint Doppler ultrasonography (DUS) is a simple, non-invasive examination, able to visualize synovitis. Its diagnostic and prognostic value in rheumatoid arthritis is well-established., Methods: Patients with serologically proven acute arbovirosis where included. Clinical examination and joint count were performed (DAS score). Ultrasound examination was performed by another clinician - experienced in joint DUS - who also performed ultrasound joint score. Joints were examined by DUS in B-mode looking for: subcutaneous infiltration, effusion, tenosynovitis, erosion and Doppler signal., Results: In our experience, joint DUS is able to detect effusions in 92.8% of painful joints, with 28.3% of the effusions emitting a high-power Doppler signal. No erosion was observed. Subcutaneous inflammatory infiltration of the ankles (aseptic cellulitis) was found in 28.6% of patients., Conclusion: Joint DUS is able to detect objective signs responsible for joint pain, which can be useful for practitioners not accustomed to this type of pathology. It also makes possible distinction between articular and periarticular manifestations., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Infection with chikungunya virus (CHIKV) causes an acute illness characterized by fever, rash, and arthralgia. However, CHIKV infection can sometimes progress to chronic arthritis or even lethal disease. CHIKV continues to cause substantial morbidity worldwide as its vector mosquitoes expand and spread. There are currently no approved vaccines or antiviral drugs available for the prevention or treatment of CHIKV. Although antibody therapy has shown promise in the prevention or treatment of CHIKV disease in preclinical models, challenges remain for implementing such therapies. Here, from the B cells of a survivor of natural CHIKV infection, we isolated ultrapotent neutralizing human monoclonal antibodies (mAbs) and encoded their sequences into mRNA molecules delivered by infusion. One human mAb, CHKV-24, was expressed to biologically significant levels in vivo after infusion of mRNAs in lipid nanoparticles in mice. We evaluated the protective capacity of CHKV-24 mAb immunoglobulin G protein or mRNA in mouse models of CHIKV infection. Treatment with CHKV-24 mRNA protected mice from arthritis, musculoskeletal tissue infection, and lethality and reduced viremia to undetectable levels at 2 days after inoculation. Infusion of macaques with CHKV-24 mRNA achieved a mean maximal mAb concentration of 10.1 to 35.9 micrograms per milliliter, with a half-life of 23 days, a level well above what is needed for protection in mice. Studies with CHKV-24 mRNA in macaques demonstrated a dose-response effect after the first dose of mRNA and maintained levels after second dose. These preclinical data with CHKV-24 mRNA suggest that it might be useful to prevent human disease., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Chikungunya virus (CHIKV) is the most common alphavirus infecting humans worldwide. Antibodies play pivotal roles in the immune response to infection. Increasingly, therapeutic antibodies are becoming important for protection from pathogen infection for which neither vaccine nor treatment is available, such as CHIKV infection. The new generation of ultra-potent and/or broadly cross-reactive monoclonal antibodies (mAbs) provides new opportunities for intervention. In the past decade, several potent human and mouse anti-CHIKV mAbs were isolated and demonstrated to be protective in vivo. Mechanistic studies of these mAbs suggest that mAbs exert multiple modes of action cooperatively. Better understanding of these antiviral mechanisms for mAbs will help to optimize mAb therapies.

Objective: Dengue and chikungunya virus diseases are becoming an increasingly important global health threats and are continuously expanding their geographical range. The study aims to investigate knowledge and diagnostic practice of dengue and chikungunya fever among healthcare workers in Moshi Municipality., Results: Most of healthcare workers heard of chikungunya and dengue 146 (71.2%) and 203 (99%) respectively. Ninety-five (46.3%) and 152 (74.1%) had good knowledge regard chikungunya and dengue respectively. One hundred and twenty-two of HCWs 122 (59.5%) reported that there is no vaccination for dengue virus. Most HCWs 199 (97.0%) reported that the absence of diagnostic tool for dengue virus lead to difficult in managing the infection. The finding of this study showed that there is insufficient knowledge regarding chikungunya while knowledge regarding dengue is relatively fair. This calls for training regarding these infections.

Between September 15 and November 11, 2017, the area of Rome was subjected to cessation of donation in an area of approximately 1,300,000 inhabitants and with a 5-day quarantine for the rest of metropolitan areas due to Chikungunya virus (CHIKV) outbreak. Quarantine was applied to red blood cell (RBC) and plasma units while platelet concentrates (PCs) were subjected to pathogen inactivation methods (PIMs). Quarantine was based on an active recall of all donors and, in case of declared absence of any symptom or illness, on release of RBC and plasma units after 5 days. Four regional centers in which PIMs were already performed were charged for PIMs for the rest of Rome's area. These centers increased by 236% their previous PIM procedures, producing additional 1425 pathogen-reduced (PR) PCs in 57 days, beside their production (996 PR PCs) for local needs. The emergency support was close to the maximal production capacity of the four centers and was successful only thanks to the limited length of emergency. No adverse events were reported by all centers through a passive hemovigilance approach and by a follow-up of approximately 4 months. None of the donors referred symptoms or illness at recall and none of the blood products were discarded after quarantine. To date, no cases of CHIKV-transmitted infection were reported in transfused patients. This experience has taught some relevant strategic and organizing aspects that should be taken into account when an infectious outbreak must be faced in a large metropolitan area., (© 2018 AABB.)

Chikungunya fever (CHIKF) is a re-emerging mosquito-borne disease caused by a virus endemic to Africa and Asia. Due to the ease with which its vectors propagate, the virus has spread to India and Europe, and more recently it arrived to the Caribbean, eventually extending into North, Central, and South America. According to the World Health Organization (WHO), the most common clinical manifestations are abrupt fever, polyarthralgia, headache, maculopapular rash, myalgia, and nausea/vomiting. Severe joint pain and stiffness have been known to incapacitate some patients from a few days to several months after infection. Fatal cases are rare, but some individuals have been known to develop severe forms of the disease that include neurological and cardiac complications and severe cutaneous manifestations. Additionally, there have been reports of infected mothers miscarrying and newborns that were infected in utero being born with congenital illnesses. Advanced age and various comorbidities have been associated with severe or atypical forms of CHIKF. Currently there are no approved vaccines for the chikungunya virus (CHIKV), and treatment aims to alleviate patient symptoms. The re emergence of the CHIKV and its spread to new places around the globe encourage the development of new preventive, diagnostic, and treatment options.

Chikungunya virus (CHIKV) is a re-emergent arthropod-borne virus (arbovirus) that causes a disease characterized primarily by fever, rash and severe persistent polyarthralgia. In the last decade, CHIKV has become a serious public health problem causing several outbreaks around the world. Despite the fact that CHIKV has been around since 1952, our knowledge about immunopathology, innate and adaptive immune response involved in this infectious disease is incomplete. In this review, we provide an updated summary of the current knowledge about immune response to CHIKV and about soluble immunological markers associated with the morbidity, prognosis and chronicity of this arbovirus disease. In addition, we discuss the progress in the research of new vaccines for preventing CHIKV infection and the use of monoclonal antibodies as a promising therapeutic strategy.

Background: Chikungunya virus causes mosquito-transmitted infection that leads to extensive morbidity affecting substantial quality of life. Disease associated morbidity, quality of life, and financial loss are seldom reported in resources limited countries, such as Bangladesh. We reported the acute clinical profile, quality of life and consequent economic burden of the affected individuals in the recent chikungunya outbreak (May to September 2017) in Dhaka city, Bangladesh., Methods: We conducted a cross-sectional study during the peak of chikungunya outbreak (July 24 to August 5, 2017) to document the clinical profiles of confirmed cases (laboratory test positive) and probable cases diagnosed by medical practitioners. Data related to clinical symptoms, treatment cost, loss of productivity due to missing work days, and quality of life during their first two-weeks of symptom onset were collected via face to face interview using a structured questionnaire. World Health Organization endorsed questionnaire was used to assess the quality of life., Results: A total of 1,326 chikungunya cases were investigated. Multivariate analysis of major clinical variables showed no statistically significant differences between confirmed and probable cases. All the patients reported joint pain and fever. Other more frequently reported symptoms include headache, loss of appetite, rash, myalgia, and itching. Arthralgia was polyarticular in 56.3% of the patients. Notably, more than 70% patients reported joint pain as the first presenting symptom. About 83% of the patients reported low to very low overall quality of life. Nearly 30% of the patients lost more than 10 days of productivity due to severe arthropathy., Conclusions: This study represents one of the largest samples studied so far around the world describing the clinical profile of chikungunya infection. Our findings would contribute to establish an effective syndromic surveillance system for early detection and timely public health intervention of future chikungunya outbreaks in resource-limited settings like Bangladesh., Competing Interests: The authors have declared that no competing interests exist.

Purpose of Review: To review the emergence, clinical features, pathogenesis, and treatment of acute chikungunya (CHIK) fever and chronic CHIK arthritis., Recent Findings: Since 2004, CHIK, an arboviral infection, has spread throughout the world, infecting millions of people. The illness occurs in two phases: an acute viremic infection followed by chronic arthritis. In less developed countries, there are limited resources and effective treatment. For acutely ill CHIK fever patients, management is symptomatic. The treatment of chronic CHIK arthritis should be determined by an understanding of pathogenesis. Is chronic CHIK arthritis a persistent viral infection or a postinfectious inflammatory process? Multiple proinflammatory cytokines, chemokines, and growth factors have been identified in chronic CHIK arthritis. Attempts to isolate CHIK virus from synovial fluid have been unsuccessful. Given pathogenetic similarities (as well as differences) compared with rheumatoid arthritis and the painful, disabling nature of the arthritis, it is not surprising that disease-modifying antirheumatic drugs such as methotrexate have begun to be used., Summary: CHIK infection has emerged with major arthritic epidemics for which evidence-based therapy is limited. But there is an opportunity to improve the treatment of chronic CHIK arthritis and, from this disease, to gain understanding of the pathogenesis and treatment of inflammatory arthritis more generally.

With population shifts, increased travel, and climate change, the spread of emerging and re-emerging infections is increasing. Although encountering a patient with an emerging infection on any given emergency department shift is unlikely, missing a diagnosis could have profound consequences for the patient, healthcare workers, and the patient's close contacts. This review provides a framework to evaluate, diagnose, and treat a returning traveler with suspected Middle East respiratory syndrome, chikungunya virus, or Zika virus-3 recently emerged infections. All may present with nonspecific viral-like symptoms and are easily missed if an appropriate travel history is not obtained. A high level of vigilance and proper disposition will enable the emergency clinician to effectively diagnose, manage, and contain these diseases. [Points & Pearls is a digest of Emergency Medicine Practice.].

In the past decade, arboviruses-arthropod-borne viruses-have been the focus of public health institutions worldwide following a spate of devastating outbreaks. Chikungunya virus, an arbovirus that belongs to the alphavirus genus, is a reemerging arthritogenic virus that has caused explosive outbreaks since 2006, notably on Réunion Island, and more recently in the Caribbean, South America, India, and Southeast Asia. The severity of arthritic disease caused by chikungunya virus has prompted public health authorities in affected countries to develop specific guidelines to tackle this pathogen. Chikungunya virus disease manifests first as an acute stage of severe joint inflammation and febrile illness, which later progresses to a chronic stage, during which patients may experience debilitating and persisting articular pain for extended periods. This review aims to provide a broad perspective on current knowledge of chikungunya virus pathogenesis by identifying key clinical and experimental studies that have contributed to our understanding of chikungunya virus to date. In addition, the review explores the practical aspects of treatment and management of both acute and chronic chikungunya virus based on clinical experience during chikungunya virus outbreaks. Finally, recent findings on potential therapeutic solutions-from antiviral agents to immunomodulators-are reviewed to provide both viral immunologists and clinical rheumatologists with a balanced perspective on the nature of a reemerging arboviral disease of significant public health concern, and insight into future therapeutic approaches to better address the treatment and management of chikungunya virus., (© 2017, American College of Rheumatology.)

Introduction: Chikungunya virus is amongst the fastest expanding vector transmissible diseases in recent years and has been causing massive epidemics in Africa, Asia, Latin America and the Caribbean. Despite human infection by this virus being first described in the 1950s, there is a lack of adequate therapeutic evaluations to guide evidence-based recommendations. The current guidelines rely heavily in specialists' opinion and experience instead of using higher rated evidence. Areas covered: A systematic review of the literature was performed- not restricted to clinical trials - reporting the therapeutic response against this infection with the intent to gather the best evidence of the treatment options against musculoskeletal disorders following chikungunya fever. The 15 studies included in the analysis were categorized considering the initiation of treatment during the acute, subacute and chronic phase. Expert commentary: This review demonstrates the complexity of chikungunya fever and difficulty of therapeutic management. This review found no current evidence-based treatment recommendations for the musculoskeletal disorders following chikungunya fever. To provide an optimal treatment that prevents perpetuation or progression of chikungunya infection to a potentially destructive and permanent condition without causing more harm is an aim that must be pursued by researchers and health professionals working with this disease.

Introduction: Chikungunya (CHIK) is a tropical arbovirus, transmitted by the female mosquito Aedes aegypti and Aedes albopictus. In Brazil, there have been cases reported since 2014. The initial manifestations of this virus are sudden onset high fever, headache, chills, rashes, myalgia and intense joint pain. Usually, CHIK presents the acute and chronic phases, the latter characterized by bilateral polyarthralgia, which can last for months or even years. During this period, autoimmune diseases can be triggered, making the picture even more complicated., Method: A systematic review was performed on the PubMed and Scielo databases in January 2017. Clinical trials, cohorts, case-control and case reports were included in the study. Expert opinions, societal consensuses and literary reviews were exclusion criteria. Studies were conducted in English, Spanish and Portuguese. The studies were descriptively analyzed and the data was grouped according to methodological similarity., Results: Twenty-four (24) articles were selected and, in compliance with the inclusion and exclusion criteria, 18 were eliminated, with six studies remaining in the present review: five clinical trials and one case report., Conclusion: When the manifestations of CHIK become chronic and, the longer they last, more complications arise. Polyarthralgia can be immaterial, distancing individuals from their daily-life activities. Anti-inflammatory drugs (either steroid or not), in addition to immunosuppressants, homeopathy and physiotherapy are measures of treatment that, according to the literature, have been successful in relieving or extinguishing symptoms. However, it is fundamental that studies of CHIK treatment be further developed.

Beginning in 2004, chikungunya virus (CHIKV) went from an endemic pathogen limited to Africa and Asia that caused periodic outbreaks to a global pathogen. Given that outbreaks caused by CHIKV have continued and expanded, serious consideration must be given to identifying potential options for vaccines and therapeutics. Currently, there are no licensed products in this realm, and control relies completely on the use of personal protective measures and integrated vector control, which are only minimally effective. Therefore, it is prudent to urgently examine further possibilities for control. Vaccines have been shown to be highly effective against vector-borne diseases. However, as CHIKV is known to rapidly spread and generate high attack rates, therapeutics would also be highly valuable. Several candidates are currently being developed; this review describes the multiple options under consideration for future development and assesses their relative advantages and disadvantages., (Copyright © 2017 American Society for Microbiology.)

Chikungunya virus (CHIKV), a mosquito-transmitted alphavirus, is recurring in epidemic waves. In the past decade and a half, the disease has resurged in several countries around the globe, with outbreaks becoming increasingly severe. Though CHIKV was first isolated in 1952, there remain significant gaps in knowledge of CHIKV biology, pathogenesis, transmission, and mechanism. Diagnosis is largely simplified and based on symptoms, while treatment is supportive rather than curative. Here we present an overview of the disease, the challenges that lie ahead for future research, and what directions current studies are headed towards, with emphasis on improvement of current animal models and potential use of 3D models., Competing Interests: The authors declare no conflict of interest.

In 2015 in Colombia, 60 pregnant women were hospitalized with chikungunya virus infections confirmed by reverse transcription PCR. Nine of these women required admission to the intensive care unit because of sepsis with hypoperfusion and organ dysfunction; these women met the criteria for severe acute maternal morbidity. No deaths occurred. Fifteen women delivered during acute infection; some received tocolytics to delay delivery until after the febrile episode and prevent possible vertical transmission. As recommended by a pediatric neonatologist, 12 neonates were hospitalized to rule out vertical transmission; no clinical findings suggestive of neonatal chikungunya virus infection were observed. With 36 women (60%), follow-up was performed 1 year after acute viremia; 13 patients had arthralgia in >2 joints (a relapse of infection). Despite disease severity, pregnant women with chikungunya should be treated in high-complexity obstetric units to rule out adverse outcomes. These women should also be followed up to treat potential relapses.

Chikungunya fever (CHIKF) is an emerging viral infection that has spread widely, along with its Aedes vectors, throughout the tropics and beyond, causing explosive epidemics of both acute illness and persistent disabling arthritis. There is an urgent need to mitigate the devastating impact of this illness, through vector control, personal protection, and possibly vaccine development. There is also a need to improve treatment for both acute illness and chronic arthritis. In this review, we will review the emergence of CHIK, what is known about pathogenesis and clinical manifestations, and then focus on current understanding of how to treat individual patients, in particular, those who develop chronic arthritis.

Competing Interests: We have read and understood The BMJ policy on declaration of interests and declare that we have no competing interests.

Chikungunya is a severe and debilitating disease. Currently, Brazil is experiencing an epidemic caused by three arboviruses, which has changed the way health professionals have diagnosed and treated infected patients. The difficulty of diagnosis and the lack of a protocol for patient treatment, which fits Brazilian health system models, have made it difficult to manage this disease. It is necessary to implement a multidisciplinary network of patient care, in which primary care units play the main role. This review aims to present current information regarding the clinical aspects and treatment of Chikungunya virus infection.