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.

Manifestaciones oftalmológicas del dengue, el zika y el chikungunya / Ophthalmic manifestations of dengue, zika and chikungunya

Las infecciones por arbovirus constituyen un reto significativo para los sistemas de salud. Cada vez se incrementa el reconocimiento de complicaciones del sistema nervioso central secundarias a ellas, lo que puede ser un dilema para su diagnóstico y tratamiento. Los arbovirus pueden alterar los mecanismos de inmunidad innatos del ojo al dañar las barreras óculo-hemáticas. En esta revisión nos propusimos caracterizar los principales hallazgos oftalmológicos de las enfermedades transmitidas por mosquito, como el dengue, el zika y el chikungunya, y su posible fisiopatología. Se realizó una búsqueda de la literatura sobre el tema en la base de datos de PubMED. En los pacientes con zika y chikungunya se reconocieron frecuentemente la conjuntivitis no purulenta y la queratitis. En los casos de dengue el edema macular y las hemorragias retinianas maculares fueron frecuentes; causaron disminución de la visión y defectos campimétricos; la vasculitis y coriorretinitis periférica podía ser asintomática si la mácula no estaba comprometida. Estuvieron implicados la trombocitopenia y otros procesos fisiopatológicos. En las enfermedades estudiadas se reportaron casos raros con parálisis de nervios oculomotores o neuritis óptica como respuesta autoinmune tardía. Recientemente se reportó el síndrome de zika congénito que incluyó múltiples anomalías del desarrollo. En los neonatos afectados se describió la atrofia macular, así como la pigmentación macular bilateral, la hipoplasia del nervio óptico, la catarata, entre otros. Existen diversas lesiones oculares secundarias a infecciones por dengue, zika y chikungunya que merecen reconocimiento, pues deterioran la función visual temporal o permanentemente(AU)

Arbovirus infections pose a significant challenge to health systems. Awareness of the secondary central nervous system complications caused by these infections is on the increase, which may be a dilemma for their diagnosis and treatment. Arboviruses may alter the innate immunity mechanisms of the eye by damaging blood-retinal barriers. The objective of this review was to characterize the main ophthalmological findings of mosquito-borne diseases, such as dengue, zika and chikungunya, and their possible physiopathology. A bibliographic search about the topic was conducted in the database PubMed. Non-purulent conjunctivitis and keratitis were frequently found in zika and chikungunya patients. Dengue cases often presented macular edema and macular retinal hemorrhage, which caused vision reduction, as well as campimetric defects. Vasculitis and peripheral chorioretinitis could be asymptomatic if the macula was not involved. Thrombocytopenia and other physiopathological processes were also present. Oculomotor nerve palsy and optic neuritis as a late autoimmune response were rarely reported in the diseases studied. Recent reports refer to congenital zika syndrome, which causes multiple developmental abnormalities. Macular atrophy, bilateral macular pigmentation, optic nerve hypoplasia and cataract, among other disorders, were described in affected neonates. A variety of ocular lesions secondary to dengue, zika and chikungunya infection deserve recognition, for they damage visual function either temporarily or permanently(AU)

Chikungunya Virus Infects the Heart and Induces Heart-Specific Transcriptional Changes in an Immunodeficient Mouse Model of Infection.

Chikungunya virus (CHIKV) is a mosquito-transmitted pathogen in family Togaviridae, genus Alphavirus. Although CHIKV is well known for its ability to cause debilitating rheumatoid-like arthritis, it has been also been observed to cause cardiovascular symptoms such as arrhythmias. Here, using samples from a previous study, we sequenced RNA from serum, kidney, skeletal muscle, and cardiac muscle from CHIKV- and mock-infected IFN-αR-/- mice using two sequencing techniques to investigate heart-specific changes in virus mutational profiles and host gene expression. Mutation rates were similar across muscle tissues although heart tissue carried heart-specific CHIKV minority variants, one of which had a coding change in the nsP3 gene and another in the 3'UTR. Importantly, heart-specific transcriptional changes included differential expression of genes critical for ion transport and muscle contraction. These results demonstrate that CHIKV replicates in the hearts of immunodeficient mice and induce heart-specific mutations and host responses with implications for cardiac pathologies.

Clinical Manifestations and Outcomes in Disease-Modifying Antirheumatic Drug-Naive Adult Patients with Chronic Chikungunya Arthritis.

Most studies on chronic chikungunya virus (CHIKV) arthritis include patients treated with disease-modifying antirheumatic drugs (DMARDs), likely altering the expression of clinical manifestations and outcome. Therefore, we sought to evaluate the clinical features and correlates in DMARD-naive patients with chronic CHIKV arthritis. We conducted a case-control study in adult patients with serologically confirmed CHIKV infection in Puerto Rico. Demographic features, clinical manifestations, comorbidities, disease activity (per Clinical Disease Activity Index [CDAI]), functional status (per Health Assessment Questionnaire Disability Index [HAQ-DI]), and pharmacologic treatment were ascertained. Patients with and without chronic CHIKV arthritis were compared. Furthermore, a sub-analysis was performed among patients with chronic CHIKV who presented with mild disease activity versus moderate-to-high disease activity at study visit. In total, 61 patients were studied; 33 patients had chronic arthritis and 28 had resolved arthritis. Patients with chronic arthritis had significantly more diabetes mellitus, chronic back pain, and fever, tiredness, and myalgias on the acute phase. The mean (SD) HAQ score was 0.95 (0.56), and 57.6% had moderate-to-high disease activity. Patients with moderate-to-high disease activity had higher scores in overall HAQ-DI and HAQ-DI categories (dressing and grooming, arising, hygiene, reaching, and activities) than in those with mild activity. In conclusion, in this group of DMARD-naive patients with chronic CHIKV arthritis, nearly 58% had moderate-to-high disease activity and had substantial functional disability. Diabetes mellitus, chronic back pain, and some manifestations on acute infection were associated with chronic CHIKV arthritis.

Chikungunya infection in pregnancy - reassuring maternal and perinatal outcomes: a retrospective observational study.

OBJECTIVE: To evaluate pregnancy and neonatal outcomes, disease severity, and mother-to-child transmission of pregnant women with Chikungunya infection (CHIKV). DESIGN: Retrospective observational study. SETTING: Grenada. POPULATION: Women who gave birth during a Chikungunya outbreak between January 2014 and September 2015 were eligible. METHODS: This descriptive study investigated 731 mother-infant pairs who gave birth during a CHIKV outbreak. Women and infants underwent serological testing for CHIKV by ELISA. MAIN OUTCOME MEASURES: Primary outcomes: composite pregnancy complication (abruption, vaginal bleeding, preterm labour/cervical incompetence, cesarean delivery for fetal distress/abruption/placental abnormality or delivery for fetal distress) and composite neonatal morbidity. RESULTS: Of 416 mother-infant pairs, 150 (36%) had CHIKV during pregnancy, 135 (33%) had never had CHIKV, and 131 (31%) had CHIKV outside of pregnancy. Mean duration of joint pain was shorter among women infected during pregnancy (µ = 898 days, σ = 277 days) compared with infections outside of pregnancy (µ = 1064 days, σ = 244 days) (P < 0.0001). Rates of pregnancy complications (RR = 0.76, P = 0.599), intrapartum complications (RR = 1.50, P = 0.633), and neonatal outcomes were otherwise similar. Possible mother-to-child transmission occurred in two (1.3%) mother-infant pairs and two of eight intrapartum infections (25%). CONCLUSION: CHIKV infection during pregnancy may be protective against long-term joint pain sequelae that are often associated with acute CHIKV infection. Infection during pregnancy did not appear to pose a risk for pregnancy complications or neonatal health, but maternal infection just prior to delivery might have increased risk of mother-to-child transmission of CHIKV. TWEETABLE ABSTRACT: Chikungunya infection did not increase risk of pregnancy complications or adverse neonatal outcomes, unless infection was just prior to delivery.

Recent Clinical and Preclinical Studies of Hydroxychloroquine on RNA Viruses and Chronic Diseases: A Systematic Review.

The rapid spread of the new Coronavirus Disease 2019 (COVID-19) has actually become the newest challenge for the healthcare system since, to date, there is not an effective treatment. Among all drugs tested, Hydroxychloroquine (HCQ) has attracted significant attention. This systematic review aims to analyze preclinical and clinical studies on HCQ potential use in viral infection and chronic diseases. A systematic search of Scopus and PubMed databases was performed to identify clinical and preclinical studies on this argument; 2463 papers were identified and 133 studies were included. Regarding HCQ activity against COVID-19, it was noticed that despite the first data were promising, the latest outcomes highlighted the ineffectiveness of HCQ in the treatment of viral infection. Several trials have seen that HCQ administration did not improve severe illness and did not prevent the infection outbreak after virus exposure. By contrast, HCQ arises as a first-line treatment in managing autoimmune diseases such as rheumatoid arthritis, lupus erythematosus, and Sjögren syndrome. It also improves glucose and lipid homeostasis and reveals significant antibacterial activity.

Role of MicroRNAs in Bone Pathology during Chikungunya Virus Infection.

Chikungunya virus (CHIKV) is an alphavirus, transmitted by mosquitoes, which causes Chikungunya fever with symptoms of fever, rash, headache, and joint pain. In about 30%-40% of cases, the infection leads to polyarthritis and polyarthralgia. Presently, there are no treatment strategies or vaccine for Chikungunya fever. Moreover, the mechanism of CHIKV induced bone pathology is not fully understood. The modulation of host machinery is known to be essential in establishing viral pathogenesis. MicroRNAs (miRNAs) are small non-coding RNAs that regulate major cellular functions by modulating gene expression. Fascinatingly, recent reports have indicated the role of miRNAs in regulating bone homeostasis and altered expression of miRNAs in bone-related pathological diseases. In this review, we summarize the altered expression of miRNAs during CHIKV pathogenesis and the possible role of miRNAs during bone homeostasis in the context of CHIKV infection. A holistic understanding of the different signaling pathways targeted by miRNAs during bone remodeling and during CHIKV-induced bone pathology may lead to identification of useful biomarkers or therapeutics.

Endemic and Epidemic Human Alphavirus Infections in Eastern Panama: An Analysis of Population-Based Cross-Sectional Surveys.

Madariaga virus (MADV) has recently been associated with severe human disease in Panama, where the closely related Venezuelan equine encephalitis virus (VEEV) also circulates. In June 2017, a fatal MADV infection was confirmed in a community of Darien Province. We conducted a cross-sectional outbreak investigation with human and mosquito collections in July 2017, where sera were tested for alphavirus antibodies and viral RNA. In addition, by applying a catalytic, force-of-infection (FOI) statistical model to two serosurveys from Darien Province in 2012 and 2017, we investigated whether endemic or epidemic alphavirus transmission occurred historically. In 2017, MADV and VEEV IgM seroprevalences were 1.6% and 4.4%, respectively; IgG antibody prevalences were MADV: 13.2%, VEEV: 16.8%, Una virus (UNAV): 16.0%, and Mayaro virus: 1.1%. Active viral circulation was not detected. Evidence of MADV and UNAV infection was found near households, raising questions about its vectors and enzootic transmission cycles. Insomnia was associated with MADV and VEEV infections, depression symptoms were associated with MADV, and dizziness with VEEV and UNAV. Force-of-infection analyses suggest endemic alphavirus transmission historically, with recent increased human exposure to MADV and VEEV in Aruza and Mercadeo, respectively. The lack of additional neurological cases suggests that severe MADV and VEEV infections occur only rarely. Our results indicate that over the past five decades, alphavirus infections have occurred at low levels in eastern Panama, but that MADV and VEEV infections have recently increased-potentially during the past decade. Endemic infections and outbreaks of MADV and VEEV appear to differ spatially in some locations of eastern Panama.

First report of Chikungunya fever in Rawalpindi, Pakistan.

BACKGROUND: Chikungunya shares many clinical features with dengue fever, but to date, no case has been reported in Rawalpindi and surrounding areas. AIMS: To detect the presence in Rawalpindi of chikungunya masquerading as dengue fever. METHODS: An observational study was conducted at Rawalpindi Medical University from July to December 2017. Patients with clinical features suggestive of dengue fever, but negative for dengue virus NS1 antigen were included and tested at the National Institute of Health Islamabad, Pakistan, for chikungunya using reverse transcription polymerase chain reaction. RESULTS: We tested 129 patients and 28 were positive for chikungunya. There were 17 (60.7%) men and 11 (39.3%) women, with a mean age of 32.53 years (range 16-60 years). All had fever at presentation. Other clinical features at presentation were noted, such as fever, chills, fatigue, headache, myalgia, arthralgia, retro-orbital pain, abdominal pain, nausea, and diarrhoea. No long-term sequelae or bleeding diatheses were seen and there was no mortality reported. CONCLUSIONS: The clinical features observed and investigated confirmed our reporting of the first case of chikungunya in Rawalpindi, Pakistan.

Increased serum levels of galectin-9 in patients with chikungunya fever.

Chikungunya fever (CHIKF) is an arboviral disease that has caused an epidemic burst of chronic inflammatory joint disease in Latin America in the last few years. Efforts are being spent in understanding the mechanisms by which it may cause such articular damage and in determining possible biomarkers of the disease. Galectins (GAL) are a family of animal lectins with an affinity for beta-galactosides. They have multiple functions including working as receptors in innate immunity and as a control for inflammatory responses in both innate and adaptive immunity. They regulate functions of immune cells, such as lymphocytes and macrophages, which have a main role in the chikungunya inflammatory process. Galectins are also involved in chronification of viral diseases, participate in the immunopathogenesis of chronic joint diseases such as rheumatoid arthritis, and have a role in inflammation in other arboviral diseases, such as dengue. Thus, we intended to determine the serum levels of galectin-1, -3, -4, -7, and -9 in patients with subacute and chronic articular manifestations of CHIKF and to evaluate their associations with clinical manifestations. We evaluated 44 patients with clinical manifestations of CHIKF and serological confirmation with IgM and/or IgG chikungunya virus (CHIKV) antibodies. Forty-nine age- and gender-matched healthy individuals served as controls. Anti-CHIKV IgM and IgG antibodies and galectins serum levels were measured by ELISA. We found higher levels of GAL-9 (patients median 2192 [1500-2631] pg/mL, controls median 46.88 [46.88-46.88] pg/mL, p < 0.0001) and lower levels of GAL-3 (patients median 235.5 [175.5-351.8] pg/mL, controls median 2236.0 [1256.0-2236.0] pg/mL, p < 0.0001) in patients than in controls. There was no statistical difference in levels of GAL-1, -4 and -7 between patients and control groups. There was no difference in GAL-9 serum levels between patients with subacute or chronic symptoms (median 2148 [1500-2722] pg/mL x 2212 [1844-2500] pg/mL, p = 0.3626). A significant association of GAL-9 with joint stiffness, both in its duration and intensity, was found. These results may reflect the participation of GAL-9 in the immunopathogenesis of the inflammatory process in chikungunya fever, as morning stiffness may reflect the systemic inflammatory process.

Chikungunya in Indonesia: Epidemiology and diagnostic challenges.

BACKGROUND: Chikungunya virus (CHIKV) is often overlooked as an etiology of fever in tropical and sub-tropical regions. Lack of diagnostic testing capacity in these areas combined with co-circulation of clinically similar pathogens such as dengue virus (DENV), hinders CHIKV diagnosis. To better address CHIKV in Indonesia, an improved understanding of epidemiology, clinical presentation, and diagnostic approaches is needed. METHODOLOGY/PRINCIPAL FINDINGS: Acutely hospitalized febrile patients ≥1-year-old were enrolled in a multi-site observational cohort study conducted in Indonesia from 2013 to 2016. Demographic and clinical data were collected at enrollment; blood specimens were collected at enrollment, once during days 14 to 28, and three months after enrollment. Plasma samples negative for DENV by serology and/or molecular assays were screened for evidence of acute CHIKV infection (ACI) by serology and molecular assays. To address the co-infection of DENV and CHIKV, DENV cases were selected randomly to be screened for evidence of ACI. ACI was confirmed in 40/1,089 (3.7%) screened subjects, all of whom were DENV negative. All 40 cases initially received other diagnoses, most commonly dengue fever, typhoid fever, and leptospirosis. ACI was found at five of the seven study cities, though evidence of prior CHIKV exposure was observed in 25.2% to 45.9% of subjects across sites. All subjects were assessed during hospitalization as mildly or moderately ill, consistent with the Asian genotype of CHIKV. Subjects with ACI had clinical presentations that overlapped with other common syndromes, atypical manifestations of disease, or persistent or false-positive IgM against Salmonella Typhi. Two of the 40 cases were possibly secondary ACI. CONCLUSIONS/SIGNIFICANCE: CHIKV remains an underdiagnosed acute febrile illness in Indonesia. Public health measures should support development of CHIKV diagnostic capacity. Improved access to point-of-care diagnostic tests and clinical training on presentations of ACI will facilitate appropriate case management such as avoiding unneccessary treatments or antibiotics, early response to control mosquito population and eventually reducing disease transmission.

Comparison of clinical presentation and out-comes of Chikungunya and Dengue virus infections in patients with acute undifferentiated febrile illness from the Sindh region of Pakistan.

BACKGROUND: Arboviruses are a cause of acute febrile illness and outbreaks worldwide. Recent outbreaks of Chikungunya virus (CHIKV) in dengue endemic areas have alarmed clinicians as unique clinical features differentiating CHIKV from Dengue virus (DENV) are limited. This has complicated diagnostic efforts especially in resource limited countries where lab testing is not easily available. Therefore, it is essential to analyse and compare clinical features of laboratory confirmed cases to assist clinicians in suspecting possible CHIKV infection at time of clinical presentation. METHODOLOGY: A prospective point prevalence study was conducted, with the hypothesis that not all patients presenting with clinical suspicion of dengue infections at local hospitals are suffering from dengue and that other arboviruses such as Chikungunya, West Nile viruses, Japanese Encephalitis virus and Zika virus are co-circulating in the Sindh region of Pakistan. Out-patients and hospitalized (in-patients) of selected district hospitals in different parts of Sindh province of Pakistan were recruited. Patients with presumptive dengue like illness (Syndromic diagnosis) by the treating physicians were enrolled between 2015 and 2017. Current study is a subset of larger study mentioned above. Here-in we compared laboratory confirmed cases of CHIKV and DENV to assess clinical features and laboratory findings that may help differentiate CHIKV from DENV infection at the time of clinical presentation. RESULTS: Ninety-eight (n = 98) cases tested positive for CHIKV, by IgM and PCR and these were selected for comparative analysis with DENV confirmed cases (n = 171). On multivariable analysis, presence of musculoskeletal [OR = 2.5 (95% CI:1.6-4.0)] and neurological symptoms [OR = 4.4 (95% CI:1.9-10.2)], and thrombocytosis [OR = 2.2 (95% CI:1.1-4.0)] were associated with CHIKV infection, while atypical lymphocytes [OR = 8.3 (95% CI:4.2-16.7)] and thrombocytopenia [OR = 8.1 (95% CI:1.7-38.8)] were associated with DENV cases at time of presentation. These findings may help clinicians in differentiating CHIKV from DENV infection. CONCLUSION: CHIKV is an important cause of illness amongst patients presenting with acute febrile illness in Sindh region of Pakistan. Arthralgia and encephalitis at time of presentation among patients with dengue-like illness should prompt suspicion of CHIKV infection, and laboratory confirmation must be sought.

Pathogenetic Potential Relating to Metabolic Activity in a Mouse Model of Infection with the Chikungunya Virus East/Central/South African Genotype.

Epidemics of the Chikungunya virus (CHIKV) from 2004 onwards were caused by the East/Central/South African (ECSA) genotype. However, the pathogenesis of the genotype infection has not been fully explained. In this study, we examined the pathogenic potential of CHIKV ECSA genotype M-30 (M-30) by comparing it with that of African genotype S-27 (S-27) in mice. Following low titer infections in type-I IFN receptor KO (A129) mice, we found that the M-30 infection caused high and acute fatality compared with the S-27 infection. M-30-infected A129 mice showed higher viral loads in their central nervous systems and peripheral organs, and increased levels of IFN-γ responses in their brains. Interestingly, M-30-infected mice did not show the hypophagia and reductions in weight which were observed in S-27-infected mice. Our observations provide a novel explanation of the pathogenic mechanisms attributed to virus proliferation, anti-type-II IFN response and metabolic activity in the CHIKV ECSA virus in mice.

Stiffness, pain, and joint counts in chronic chikungunya disease: relevance to disability and quality of life.

INTRODUCTION/OBJECTIVES: To characterize the importance of musculoskeletal stiffness in a cohort of chikungunya patients with chronic joint symptoms. METHOD: Eighty-two patients were followed up 3 years after chikungunya infection. Tender and swollen joint counts, a pain intensity scale, Health Assessment Questionnaire-Disability Index (HAQ-DI), and the EuroQol EQ-5D quality of life instrument were completed. A musculoskeletal stiffness questionnaire provided scores for overall stiffness and its components: stiffness severity, physical impact, and psychosocial impact. RESULTS: Patients had a mean age 51 ± 14 years. Sixty-seven patients were still experiencing chronic arthralgia. Musculoskeletal stiffness was reported by 43/67 patients with arthralgia and 3/15 patients without arthralgia. A physical impact of stiffness was reported by 87% patients and psychosocial impact by 71% patients. Mean tender joint count in patients reporting arthralgia was 6 ± 7, mean pain intensity 65 ± 20 out of 100, mean HAQ-DI was 0.54 ± 0.52, and mean EQ-VAS global health perception was 68 ± 62 out of 100. Stiffness severity was correlated with tender joint counts (ρ = 0.46) and pain intensity (ρ = 0.40). All three measures were equally well correlated with the EuroQol-VAS global health perception. Pain and tender joints were better correlated with the HAQ-DI (ρ = 0.68 and ρ = 0.63), but stiffness was more strongly correlated with several quality of life domains, including mobility. Swollen joints were a poor predictor of outcomes. CONCLUSIONS: Musculoskeletal stiffness following chikungunya infection is distinct from arthralgia. It does not always occur in the same patients or with a corresponding intensity. Joint pain and stiffness may be independently associated with disability and quality of life assessments.

Cytokines and chemokines triggered by Chikungunya virus infection in human patients during the very early acute phase.

BACKGROUND: The immune response against the Chikungunya virus (CHIKV) during the very early acute phase is not fully elucidated. Therefore we explored the cytokine and chemokine profile triggered by CHIKV in infected patients. METHODS: Cytokines, chemokines and C5a anaphylatoxin were analysed in serum from CHIKV-infected patients during the viraemic phase (mean 2.97±1.27 d after illness onset) compared with a healthy group. RESULTS: CHIKV-infected patients had a significant increase of interferon-α (IFN-α), interleukin-6 (IL-6), interleukin-8 (CXCL8/IL-8), interleukin-10 (IL-10), interferon-γ (IFN-γ), monokine induced by interferon-γ (CXCL9/MIG), monocyte chemoattractant protein-1 (CCL2/MCP-1), interferon-γ-induced protein-10 (CXCL10/IP-10) and complement C5a anaphylatoxin. CONCLUSIONS: The very early acute immune response triggered against CHIKV leads to an increase in pro-inflammatory immune mediators such as IFN-γ and its induced chemokines, and a high level of C5a anaphylatoxin as a result of complement activation.

Brief report: the disability of chronic chikungunya arthritis.

In 50% of patients, chikungunya fever (CHIKF) is followed by arthritic pain that is often chronic, painful, and disabling. To better define the spectrum of pain and disability in chronic CHIK arthritis (CCA), we evaluated 35 consecutive CCA patients seen in a Brazilian rheumatology clinic, using a pain Visual Analog Scale and the Health Assessment Questionnaire Disability Index. In our patients, pain and disability levels were of the same magnitude as are seen in other serious rheumatic diseases. The mean score for 19 patients with moderate disability was 1.42± 0.20 (median 1.37). The median HAQ-DI score for the entire group was 1.25. These findings underscore the morbidity imposed by CCA and the urgent need for improvements in management.

Inhibition of Interleukin-1ß Signaling by Anakinra Demonstrates a Critical Role of Bone Loss in Experimental Arthritogenic Alphavirus Infections.

OBJECTIVE: Arthritogenic alphaviruses, such as Ross River virus (RRV) and chikungunya virus (CHIKV), particularly affect joints of the extremities and can lead to debilitating and potentially chronic polyarthritis/polyarthralgia. The innate immune response of the host plays a crucial role in inducing proinflammatory host factors, leading to tissue destruction and bone loss in the joints. This study was performed to assess how the inhibition of interleukin-1ß (IL-1ß) signaling using the clinical rheumatoid arthritis drug anakinra influences bone loss in mice with arthritogenic alphavirus infections. METHODS: Mice (n = 5 per group) were infected with RRV or CHIKV and then treated with anakinra. Weight gain and disease severity were measured, tissue viral titers were determined, and histologic changes in joint tissues were assessed. RESULTS: Anakinra therapy reduced RRV- and CHIKV-induced bone loss in this murine model (P < 0.001 and P < 0.05, respectively). Histologic analysis of the knee joint showed that treatment with anakinra decreased epiphyseal growth plate thinning, loss of epiphyseal bone volume, and osteoclastogenesis in the tibia. Importantly, pharmacologic IL-1 receptor (IL-1R) blockade did not improve other clinical features, including disease score, weight loss, or viremia. CONCLUSION: The present findings suggest that anakinra therapy may reduce bone loss in experimental murine models of RRV and CHIKV. Further investigations are needed to assess the potential therapeutic benefits of anakinra in patients with arthritogenic alphavirus disease.

Spectrum of neurological complications in chikungunya fever: experience at a tertiary care centre and review of literature.

Chikungunya (CHIK) has re-emerged as a potential neurotropic virus, with outbreaks recently being reported from many parts of India. The present study was conducted to study the spectrum and outcome of neurological complications in patients of CHIK during the 2016 outbreak in Delhi. A total of 42 cases seropositive for IgM CHIK antibodies by MAC-ELISA and developing neurological complications were enrolled. The male:female ratio was 1:2 (age range = 18-90 years). The neurological manifestations observed were encephalitis (n = 12), bulbar palsy (n = 3), acute disseminated encephalomyelitis (n = 1), cerebellitis (n = 1), myelopathy (n = 1), radiculoneuropathy (n = 3), carpal tunnel syndrome (n = 9) and tremors (n = 1). Ten patients reported worsening of pre-existing neuropathic symptoms of diabetic peripheral neuropathy (n = 4) and carpal tunnel syndrome (n = 6). One patient had aggravation of myasthenia gravis leading to respiratory failure. The majority of patients (n = 32) showed a good outcome; ten had a poor prognosis, out of which four died, all from the encephalitis group, particularly the elderly with co-morbidities.

Evaluation of pain, functional capacity and kinesiophobia in women in the chronic stage of chikungunya virus infection: A cross-sectional study in northeastern Brazil.

Arboviral diseases have been considered a global public health problem due to their growing territorial dispersion and impact on the population around the world. Individuals affected by the chikungunya virus go through an acute febrile illness associated with severe pain and long-lasting polyarthralgia. After the initial stage, infected individuals may progress to the chronic stage, which has an epidemic character and a high rate of disability and reduced mobility, impacting negatively on their quality of life. The aim of this study was to evaluate the relationship between pain, functional capacity, and kinesiophobia in individuals in the chronic stage of chikungunya virus infection. A cross-sectional study was conducted in the city of Natal, in Rio Grande do Norte, Brazil, between July and September 2018. The participants were 59 women in the chronic stage of chikungunya virus infection. Data were collected in at physical therapy outpatient clinic of the Federal University of Rio Grande do Norte (UFRN), using a socio-demographic questionnaire, the Visual Analogue Scale (VAS), the Nordic Musculoskeletal Questionnaire (NMQ), the Brief Pain Inventory (BPI), the Health Assessment Questionnaire (HAQ), and the Tampa Scale for Kinesiophobia (TSK). Descriptive statistics and bivariate analysis of the time data were conducted by simple regression. The participants' mean age was just over 50 years and average duration of virus infection was 21.54 months. Most participants had moderate to severe pain intensity that more frequent in the ankle and wrist joints. Functional capacity was low, and there was moderate fear of performing exercises and activities of daily living. Duration of infection was associated with increased pain intensity and loss of functional capacity. We can conclude that women in the chronic stage of chikungunya infection have significant pain, reduced functional capacity, and fear of performing common movements of daily living.

Clinical and Laboratory Characteristics of an Acute Chikungunya Outbreak in Bangladesh in 2017.

From April to September 2017, Bangladesh experienced a huge outbreak of acute Chikungunya virus infection in Dhaka. This series describes the clinical and laboratory features of a large number of cases (690; 399 confirmed and 291 probable) suffered during that period. This observational study was carried out at Dhaka Medical College Hospital, Bangladesh. The median age of the patients at presentation was 38 years (IQR 30-50) with a male (57.3%) predominance. Hypertension and diabetes were the most common comorbidities. The mean (±SD) duration of fever was 3.7 (±1.4) days. Other common manifestations were arthralgia (99.2%), maculopapular rash (50.2%), morning stiffness (49.7%), joint swelling (48.5%), and headache (37.6%). Cases were confirmed by anti-chikungunya IgG (173; 43.3%), IgM (165; 42.3%), and reverse transcription polymerase chain reaction (44; 11.0%). Important laboratory findings include high erythrocyte sedimentation rate (156; 22.6%), raised serum glutamic pyruvic transaminase (73; 10.5%), random blood sugar (54; 7.8%), leukopenia (72; 10.4%), thrombocytopenia (41; 5.9%), and others. The oligo-articular (453; 66.1%) variety of joint involvement was significantly more common compared with the poly-articular (237; 34.5%) variety. Commonly involved joints were the wrist (371; 54.1%), small joints of the hand (321; 46.8%), ankle (251; 36.6%), knee (240; 35.0%), and elbow (228; 33.2%). Eleven cases were found to be complicated with neurological involvement and two of them died. Another patient died due to myocarditis. Public health experts, clinicians, and policymakers could use the results of this study to construct the future strategy tackling chikungunya in Bangladesh and other epidemic countries.