Immunological impact of cytokines on the chikungunya virus pathophysiology: A literature narrative review.

The chikungunya virus (CHIKV) is a member of the genus Alphavirus, family Togaviridae. CHIKV causes an acute systemic febrile condition, accompanied by severe polyarthralgia, intense muscle pain, and maculopapular exanthema, which may still occur in many patients. In rare cases, unusual symptoms may occur, eventually worsening the condition and resulting in a fatal outcome. It is a single-stranded, non-segmented RNA virus with a genome of approximately 11,805 nucleotides that organises a genetic and molecular chain that encodes non-structural proteins (nsP1, nsP2, nsP3, nsP4) and structural proteins (E3, E2, 6K, and E1). The fundamental role of immune response in the evolution of the disease is known. Understanding the role of immune response in the pathogenesis of CHIKV infection is challenging. In this context, innate and adaptive immune responses establish a connective interface that induces the production of various mediators that modulate the strategy of inhibiting viral replication. However, the immune escape articulated by the virus indicates that the action of pro-and anti-inflammatory cytokines contributes to the worsening of the disease and potentiates tissue damage with joint involvement. In this review, we discuss the role of the primary pro-and anti-inflammatory cytokines in the immunopathological processes of chikungunya fever.

The relationship between chikungunya virus and the kidneys: A scoping review.

Several atypical forms of chikungunya fever (CHIK) have been described, including neurological, cardiac and renal involvement. These forms may be related to high morbidity and mortality rates. This scoping review based on the PubMed, Scopus, and WOS databases aims to identify and summarise all the available evidence regarding the clinical and histopathological presentations and risk factors associated with kidney injury related to CHIK, as well as the clinical impact. Thus, a total of 54 papers were selected from 1606 initial references after applying the defined inclusion criteria. Data on the association between kidney injury and CHIK are scarce, with studies only conducted in the acute phase of the disease, lacking further characterisation. Kidney injury incidence in hospitalised patients using the Kidney Disease Improving Global Outcomes criteria varies from 21% to 45%, being higher among patients with atypical and severe manifestations. Although acute kidney injury does not seem to be related to viraemia, it may be related to higher mortality. Few studies have described the renal histopathological changes in the acute phase of CHIK, with prevalent findings of acute interstitial nephritis with mononuclear infiltrate, glomerular congestion and nephrosclerosis. Only one study assessed the kidney function of patients in the subacute and chronic phases of CHIK. Additionally, individuals with comorbidities, including chronic kidney disease, may be among those with a greater risk of presenting worse outcomes when affected by CHIK. The results described herein may contribute to better understand the relationship between the kidneys and chikungunya virus.

Contributions of musculoskeletal rehabilitation in patients after chikungunya fever: a systematic review.

INTRODUCTION: Chikungunya fever is an infection transmitted by the Chikungunya virus (CHIKV), which is an arbovirus that is transmitted by the mosquitoes Aedes aegypti and Aedes albopictus. The most common sequelae caused by CHIKV are chronic musculoskeletal pain, nerve damage, joint deformation and functional impairment. OBJECTIVE: To systematically identify the literature on the contributions of physiotherapy in the treatment of patients with CHIKV sequelae. MATERIALS AND METHODS: Systematic review of the literature, guided by the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The databases used were PUBMED, LILACS, Scielo and PEDro. Experimental studies and/or full case studies published without language restriction or publication data were included, in which they stood out as contributions of musculoskeletal functional rehabilitation in the treatment of patients with the condition in question. Analytical observational studies, editorial letters, review protocols, reflective studies, literature reviews and articles that do not have an abstract and/or full text available online were excluded. RESULTS: The search in the databases was carried out between July and August 2022. A total of 4,782 articles were found on the platforms used and 10 articles from the gray literature search. After the duplicate analysis, 2,027 studies were excluded, leaving 2,755 articles that had their titles and abstracts read, of which 600 articles were selected for full reading. After this step, a final sample of 13 articles was eligible for this review. FINAL CONSIDERATIONS: The most consolidated approaches used in the literature demonstrate that kinesiotherapy, associated or not with electrothermophototherapy, the pilates method and auriculotherapy are useful resources in the treatment of these individuals, significantly inspired by pain relief, improved quality of life and of functionality.

Protective Effects of Caffeine on Chikungunya and Zika Virus Infections: An in Vitro and in Silico Study.

Infection by viruses Chikungunya (CHIKV) and Zika (ZIKV) continue to be serious problems in tropical and subtropical areas of the world. Here, we evaluated the antiviral and virucidal activity of caffeine against CHIKV and ZIKV in Vero, A549, and Huh-7 cell lines. Results showed that caffeine displays antiviral properties against both viruses. By pre-and post-infection treatment, caffeine significantly inhibited CHIKV and ZIKV replication in a dose-dependent manner. Furthermore, caffeine showed a virucidal effect against ZIKV. Molecular docking suggests the possible binding of caffeine with envelope protein and RNA-dependent RNA polymerase of CHIKV and ZIKV. This is the first study that showed an antiviral effect of caffeine against CHIKV and ZIKV. Although further studies are needed to better understand the mechanism of caffeine-mediated repression of viral replication, caffeine appears to be a promising compound that could be used for in vivo studies, perhaps in synergy with other compounds present in daily beverages.

Epidemiological and clinical characteristics of the chikungunya outbreak in Ruili City, Yunnan Province, China.

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

Epidemiological burden of Chikungunya fever in Brazil, 2016 and 2017.

OBJECTIVES: To describe Chikungunya fever (CHIKF) cases and estimate the burden of the disease in Brazil between 2016 and 2017. METHODS: The first stage of this study consisted of a descriptive epidemiological study with estimations of incidence, mortality and case-fatality rates for each Brazilian state. The second stage provided estimates of the disease burden using DALY, an indicator that aggregates measures of morbidity (years lived with disability - YLD) and mortality (years of life lost - YLL) into a single value. RESULTS: In Brazil, the incidence rate in 2016 was 114.70 per 100,000 inhabitants, while the mortality rate was 0.15 per 100,000, for a case-fatality rate of 0.13%. In 2017, these figures were 87.59 and 0.12 per 100,000 inhabitants and 0.14%, respectively. The estimated CHIKF burden for Brazil in 2016 was 77,422.61 DALY or 0.3757 per 1000 inhabitants. In 2016, the YLL share of DALY was 10.04%, with YLD accounting for the remaining 89.96%. In 2017, the estimated burden was 59,307.59 DALY or 0.2856 per 1000 inhabitants, with YLL accounting for 9.65% of the total and YLD for 90.35%. CONCLUSION: CHIKF causes a significant disease burden in Brazil. The chronic phase of CHIKF is responsible for the largest portion of DALY. Deaths from CHIKF are a significant component of the disease burden, with YLL accounting for approximately 10% of the total DALY value.

Chikungunya Fever: Comparison Study of Synovitis and Tenosynovitis of the Hands and Wrists Using Physical Examination, Ultrasound, and MRI Findings.

OBJECTIVES: To compare musculoskeletal changes on a physical examination (PE), ultrasound (US) and magnetic resonance imaging (MRI) of the hands and wrists of patients with Chikungunya fever (CF). METHODS: The sample consisted of 30 patients in the chronic phase of CF. The sites analyzed were the interphalangeal (IP), metacarpophalangeal (MCP) and wrist/mediocarpal (WMC) joints and periarticular soft tissue. The interval between the PE and imaging tests was 7 days, and the interval between US and MRI was 2 days. The kappa coefficient was calculated to estimate the agreement between the PE and US and MRI findings and between the US and MRI findings. RESULTS: Significant agreement was observed between PE and US in the diagnosis of synovitis. The only statistically significant agreement between US and MRI was the finding of flexor tenosynovitis; the agreement was moderate. CONCLUSIONS: US has great potential for use in diagnosing synovitis suspected based on a PE. The limited agreement observed between US and MRI, in turn, may suggest a complementary role of these methods.

Long-Term Neurodevelopmental Outcomes of Neonatal Chikungunya: Follow-Up of a Series of Cases Till 1 Year.

OBJECTIVES: Short- or long-term neurodevelopmental outcomes of Neonatal Chikungunya infection haven't been well described. In this study, we describe neurodevelopmental outcomes of a series of 13 infants. METHODS: Study was conducted over a period of 1 year in high-risk follow-up clinic. Follow-up visits were conducted at 3, 6, 9, 12 ± 3 months. PRIMARY OUTCOME: Development Quotient by Developmental Assessment Scales for Indian Infants. Secondary outcome: growth/anthropometric assessment, neuromotor/neurosensory and re-hospitalization rate. RESULTS: DASII was <85 in three infants. Two other had expressive speech delay. Two, three and four babies had head circumference, length and weight below third centile, respectively. Two infants had persistent hypertonia and one had hypotonia. Two infants developed strabismus. Two infants had seizures persisting at 12 months requiring re-hospitalization. CONCLUSION: Neonatal Chikungunya infection portends a poor neurodevelopmental outcome at 1 year of age. Careful neurodevelopmental follow-up is required for identification and management of sequelae.

Mucocutaneous manifestations of Chikungunya fever, an experience of tertiary care hospital.

OBJECTIVE: To determine the frequencies of mucocutaneous manifestations of chikungunya fever, and to determine the association of positive serology with manifestations. METHODS: The observational cross-sectional study was conducted at the Department of Dermatology, Jinnah Postgraduate Medical Centre, Karachi, from May 15, 2018, to January 15, 2019, and comprised patients who presented with early and late manifestations of chikungunya fever. Different cutaneous manifestations were confirmed by a consultant dermatologist. Data was analysed using SPSS 23. RESULTS: Of the 67 patients, 46(68.7%) were females and 21(31.3%) were males. The overall mean age was 30.24±7.89 years. Hyperpigmentation was the most frequent finding 31(46%), followed by maculopapular rashes and oral ulcers in 17(25%) each, and diffuse hair fall in 14(20%). There was no significant association between clinically suspected cases and serology-positive patients. CONCLUSIONS: Chikungunya fever presented with unusual mucocutaneous findings, some of which remained present months or even years after the onset of chikungunya fever.

Pilates method in the treatment of patients with Chikungunya fever: a randomized controlled trial.

OBJECTIVE: The aim of this study was to evaluate the effects of the Pilates method on the reduction of pain, improvement of joint function, and quality of life of patients with chronic Chikungunya fever. DESIGN: This is a randomized, controlled, blind trial for the evaluators. SETTING: The study was conducted at the Advanced Laboratory in Physical Education and Health at Federal University of Pernambuco, Brazil. SUBJECTS: A total of 51 patients were allocated randomly and divided into 2 groups: a Pilates group (26 patients) and a control group (25 patients). After 12 weeks, 4 patients in the Pilates group and 5 in the control group were lost to follow-up. INTERVENTION: The Pilates group performed 24 Pilates method intervention sessions; the control group continued to receive standard clinical treatment at the outpatient clinic. MAIN MEASURES: The main measures were as follows: visual analogue scale (VAS) for pain, functional capacity evaluated by Health Assessment Questionaire (HAQ), quality of life measured by the 12-Item Short-Form Health Survey (SF-12), and range of joint motion by goniometry. RESULTS: After 12 weeks, patients in the Pilates group presented lower VAS (P < 0.001), lower HAQ scores (P < 0.001), and higher quality-of-life scores (P < 0.001) compared with the control group. We found statistically significant results for the Pilates group in the range of movement for shoulder, knee, ankle, and lumbar spine (P < 0.001). In the intragroup analysis, there was a significant improvement in all outcomes evaluated. CONCLUSION: In this study, patients undertaking Pilates method for 12 weeks had less pain, better function and quality of life, and increased range of joint movement.

[Analysis on the epidemiology and etiology characteristics of first imported Chikungunya fever case in Henan Province in 2017].

To study the epidemiology and etiology characteristics of first imported Chikungunya fever case in Henan province, China, 2017. The patient was confirmed by Chikungunya virus (CHIKV) infected as CHIKV ribonucleotide was continuously detected in his serum specimens. BHK-21 cell line was used for virus isolation, the strain was named CHIKV/Henan001/2017. CHIKV/Henan001/2017 belonged to genotype ECSA. The highest ribonucleotide homology sequence of highly conserved region E1 with CHIKV/Henan001/2017 was hk02 strain (99.8%), who was an imported strain to Hong Kong, China, 2016. Epidemiological information and laboratory testing confirmed it was an imported Chikungunya fever case in Henan province, 2017. No secondary case has been reported.

Secondary lymphedema of limbs and chikungunya fever.

Certain systemic viral infections can be related to development of vascular complications, such as deep venous thrombosis and lymphedema of lower and upper limbs. These links have been well-established in patients with human immunodeficiency virus (HIV), hepatitis C, or influenza. Recently introduced into the American continent (2013), chikungunya virus is an arbovirus transmitted by mosquitoes of the Aedes genus and is the etiologic agent of chikungunya fever (CF), but its relationship to these vascular complications has not yet been consolidated. However, the CF outbreak that occurred during 2015 and 2016 resulted in the first cases described in the medical literature of acute and chronic vascular complications secondary to infection by this arbovirus. In this report, we describe the case of a patient who developed lymphedema of upper and lower limbs after an episode of CF.

Severe Manifestations of Chikungunya Fever in Children, India, 2016.

Chikungunya is a relatively benign disease, and a paucity of literature on severe manifestations in children exits. We describe a cohort of pediatric chikungunya fever patients in New Delhi, India, who had severe sepsis and septic shock, which can develop during the acute phase of illness.

Chikungunya fever: General and oral healthcare implications.

Chikungunya virus (CHIKV) was first isolated in humans in 1952, following an epidemic in Tanzania. The origin of the name means "to bend forward or become contorted," in reference to the posture adopted by patients due to the joint pain that occurs during the infection. Epidemiology data suggest that by the end of 2015, about 1.6 million people had been infected with CHIKV. The acute period of the disease is characterized by high fever, myalgia, joint pain, and severe and disabling polyarthritis, sometimes accompanied by headache, backache, and maculopapular rash, predominantly on the thorax. Around half of the patients will progress to the subacute and chronic phases, that is manifested by persistent polyarthritis/polyarthralgia, accompanied by morning stiffness and fatigue, which could remain for years. Oral features may include gingivitis possibly as a consequence of arthralgia of the hands leading to limited oral health measures as well as burning sensation and oral mucosal ulceration. Treatment in the acute phase includes acetaminophen, and weak opioids (tramadol or codeine) should be used in cases of severe or refractory pain. For patients who have progressed to the subacute stage and who have not had notable benefit from common analgesics or opioids, NSAIDs, or adjunctive pain medications (anticonvulsants or antidepressants) may be of benefit. In patients with moderate-to-severe musculoskeletal pain or in those who cannot be given or tolerate NSIADs or opiates, prednisolone should be prescribed.

Ultrasonography of Hands and Wrists in the Diagnosis of Complications of Chikungunya Fever.

The purpose of this series was to describe the ultrasonographic and radiographic manifestations of changes to the hands and wrists in 50 patients with chronic musculoskeletal symptoms secondary to Chikungunya fever during the 2016 outbreak that occurred in Rio de Janeiro, Brazil. Most of the plain radiographs were normal (62%). The most common ultrasonographic findings were small joint synovitis (84%), wrist synovitis (74%), finger tenosynovitis (70%), and cellulitis (50%). In most cases, power Doppler did not show an increase in synovial vascular flow. The plain radiographs showed no specific findings, whereas the ultrasound images revealed synovial compromise and neural thickening.

Chikungunya Virus: History, Geographic Distribution, Clinical Picture, and Treatment.

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.

Ocular Symptoms and Signs of Chikungunya Fever in Puerto Rico.

OBJECTIVE: To determine what ocular symptoms and signs are most common and if there are any associations with comorbid conditions in patients with Chikungunya fever. METHODS: A retrospective data review and analysis of the ocular symptomatology of 139 patients with Chikungunya fever who visited a local emergency room from August through September 2014. Frequencies were calculated, and Pearson's chisquare test employed. All the patients were confirmed as having Chikungunya with IgM (ELISA) before admittance into the study. RESULTS: Of the 139 patients, 42 (30.2%) had red eyes, 27 (19.4%) had conjunctivitis, and 13 (9.4%) had symptoms related to anterior uveitis, such as unilateral red eye, ciliary flush, or irregular pupil(s). Patients with a history of diabetes, hypertension, or cancer were more likely to have both red eyes (p = 0.033) and the symptomatology of anterior uveitis (p = 0.006), while patients with nausea or vomiting were more likely to have red eyes only (p = 0.001). CONCLUSIONS AND RELEVANCE: Red eyes, conjunctivitis, and anterior uveitis occur frequently in patients with Chikungunya fever. Systemic diseases, such as diabetes, hypertension, and cancer, may increase the risk of such ocular manifestations. Routine ophthalmic evaluation is warranted in patients with these medical conditions. The relevance of this study lies in the fact that this disease remains an important public health issue, since such ocular sequelae as may be present can range from mild to severe, either as an acute or a delayed manifestation.

[Mosquito-transmitted infections]. / Infektionen durch Stechmücken.

Mosquito-transmitted diseases represent one of the greatest health risks when traveling to tropical and sub-tropical countries. Only Japanese encephalitis and yellow fever can be avoided by inoculation, and only malaria can be prevented by chemoprophylaxis. Exposure prophylaxis is the only protection against all other mosquito-born diseases. These infections need to be carefully considered in the differential diagnosis of returning travelers, taking current epidemiology into account. This review discusses common infectious diseases and the options for their diagnosis and therapy.

Chikungunya Fever in Traveler from Angola to Japan, 2016.

Simultaneous circulation of multiple arboviruses presents diagnostic challenges. In May 2016, chikungunya fever was diagnosed in a traveler from Angola to Japan. Travel history, incubation period, and phylogenetic analysis indicated probable infection acquisition in Angola, where a yellow fever outbreak is ongoing. Thus, local transmission of chikungunya virus probably also occurs in Angola.

Persistent Arthralgia Associated with Chikungunya Virus Outbreak, US Virgin Islands, December 2014-February 2016.

After the 2014-2015 outbreak of chikungunya virus in the US Virgin Islands, we compared the prevalence of persistent arthralgia among case-patients and controls. Prevalence was higher in case-patients than controls 6 and 12 months after disease onset. Continued vaccine research to prevent acute illness and long-term sequelae is essential.