Chronic Chikungunya Research Articles

Impact of chronic illness caused by chikungunya fever on quality of life and functionality.

Chikungunya fever compromises the functionality and quality of life in the affected individuals, even one year after the acute phase of the disease. Chronically affected people experience direct impairment in performing daily activities, along with a risk of developing other morbidities. ◼ Even after a year, chikungunya fever-affected people experience damage to their physical and mental health. ◼ Positive screening for depression risk was 13.5 times more likely in chronically affected. ◼ Patients with chronic chikungunya fever had a 76 times higher risk of walking impairments. To evaluate the impact of chronic illness caused by chikungunya fever on the quality of life and functionality of affected individuals. A cross-sectional and comparative study was conducted in which two groups were investigated: a Chikungunya Group comprising 25 patients with chronic fever screened after 1 year of illness via a telephonic survey, and a Healthy Group comprising 25 healthy individuals matched for sex and age by face-to-face interview. The Stanford HAQ 20-Item Disability Scale (HAQ) and the Short Form Health Survey (SF-12) questionnaires were administered to both groups. Generalized Linear Models, Pearson χ2 tests, and odds ratios were used to evaluate the test results. Significant differences in functional capacity and quality of life were observed between the Chikungunya and Healthy Groups. The chance of some impairment in functionality was also much higher in the Chikungunya Group in four of the HAQ categories, especially in the "walking" category (adjusted OR= 109.40). Further, the Chikungunya Group had a higher chance of presenting a below-average score in the mental component summary of the SF-12 (adjusted OR= 16.20) and of being positive in depression risk screening (adjusted OR= 34.57). Even one year after the acute phase, chikungunya fever can compromise the functionality and quality of life in affected individuals, with direct impairment in performing daily activities. Studies and therapeutic plans for chikungunya fever should consider the long-term impacts of this disease.

Chikungunya Arthritis Treatment with Methotrexate and Dexamethasone: A Randomized, Double-blind, Placebo-controlled Trial.

Chikungunya fever is a reemerging epidemic disease caused by a single-stranded RNA alphavirus transmitted throughout by Aedes mosquitoes. Chikungunya virus infection is a biphasic disease in which 72% to 95% of affected individuals manifest acute chikungunya fever. Following the acute phase, more than 40% of affected individuals develop arthritis, often lasting more than 3 months, referred to as chronic chikungunya arthritis, which frequently mimics rheumatoid arthritis. This study aimed to evaluate the efficacy and safety of treatment of chronic chikungunya arthritis with methotrexate and dexamethasone in a randomized, double-blind, placebo-controlled clinical trial. The patients were reassessed for treatment response by the DAS28-ESR, tender joint count and swollen joint count, Patient Global Assessment, and for secondary measures, including the Health Assessment Questionnaire Disability Index and Pain Visual Analog Scale. Thirty-one subjects were randomized (placebo, n = 16; methotrexate, n = 15); 27 completed treatment and 4 discontinued during the 8-week blinded period. Among the participants, 96.8% were female, with mean ± SD age was 52.9 ± 13. The mean ± SD disease duration prior to treatment was 220.9 ± 51.2 days. At 8 weeks, methotrexate-treated subjects showed a greater numerical trend towards improvement, but there were no significant differences between methotrexate- dexamethasone group and dexamethasone (placebo) group. In this relatively small cohort, all of whom received background dexamethasone, there was a greater numerical improvement trend in prespecified outcome measures, but methotrexate in combination with dexamethasone was not superior to dexamethasone in chronic chikungunya arthritis.

Chikungunya-virus-specific CD4+ T cells are associated with chronic chikungunya viral arthritic disease in humans

Abstract Chikungunya virus (CHIKV) is a mosquito-borne Alphavirus that causes recurrent outbreaks in tropical and subtropical regions of the world. In the first 2-7 days of infection, most individuals experience high fever, skin rash and joint pain and swelling. However, about 30-60% of the infected individuals, primarily middle-age females, develop debilitating chronic arthritis-like symptoms such as joint pain, muscle aches and edema. Despite ongoing treatment and vaccine development efforts, the immune responses to CHIKV in humans remain largely understudied. In this study, we tested peripheral blood mononuclear cells (PBMCs) collected from a cohort of 39 individuals diagnosed with CHIKV disease during the 2014-2015 epidemic in Colombia against pools of overlapping sequentially spanning the entire CHIKV genome. Using high-resolution spectral flow cytometry, we detected robust CHIKV-specific CD4+ T cell responses, but not CD8+ T cell responses in the periphery. Patients experiencing chronic symptoms displayed a significantly higher abundance of CHIKV-specific memory CD4+ T cells, compared to their recovered counterparts. Furthermore, these CD4+ T cells displayed a significantly lower Th1 phenotype but were enriched in the Th17 phenotype, with the predominant production of TNFɑ. Overall, our work demonstrates that CD4+ T cells play a pivotal role in the pathogenesis of CHIKV and provides insight into possible therapeutic options.

Cytokine and T cell responses in post-chikungunya viral arthritis: A cross-sectional study.

To define the relationship between chronic chikungunya post-viral arthritis disease severity, cytokine response and T cell subsets in order to identify potential targets for therapy. Participants with chikungunya arthritis were recruited from Colombia from 2019-2021. Arthritis disease severity was quantified using the Disease Activity Score-28 and an Arthritis-Flare Questionnaire adapted for chikungunya arthritis. Plasma cytokine concentrations (interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ and tumor necrosis factor (TNF)) were measured using a Meso Scale Diagnostics assay. Peripheral blood T cell subsets were measured using flow cytometry. Among participants with chikungunya arthritis (N = 158), IL-2 levels and frequency of regulatory T cells (Tregs) were low. Increased arthritis disease activity was associated with higher levels of inflammatory cytokines (IL-6, TNF and CRP) and immunoregulatory cytokine IL-10 (p<0.05). Increased arthritis flare activity was associated with higher Treg frequencies (p<0.05) without affecting T effector (Teff) frequencies, Treg/Teff ratios and Treg subsets. Finally, elevated levels of IL-2 were correlated with increased Treg frequency, percent Tregs out of CD4+ T cells, and Treg subsets expressing immunosuppressive markers, while also correlating with an increased percent Teff out of live lymphocytes (p<0.05). Chikungunya arthritis is characterized by increased inflammatory cytokines and deficient IL-2 and Treg responses. Greater levels of IL-2 were associated with improved Treg numbers and immunosuppressive markers. Future research may consider targeting these pathways for therapy.

Anodal tDCS over the motor cortex improves pain but not physical function in chronic chikungunya arthritis: Randomized controlled trial

BackgroundChikungunya 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. ObjectiveTo 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. MethodsIn 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. ResultsThere 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. ConclusiontDCS 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 RegistrationBrazilian Registry of Clinical Trials (ReBEC): RBR-245rh7.

Chronic chikungunya disease (CCD): clinical insights, immunopathogenesis and therapeutic perspectives.

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.

Chikungunya seroprevalence, force of infection, and prevalence of chronic disability after infection in endemic and epidemic settings: a systematic review, meta-analysis, and modelling study

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

Detection of musculoskeletal inflammatory lesions in patients with chronic chikungunya infection using 3T whole-body magnetic resonance imaging.

Musculoskeletal inflammatory lesions in chronic Chikungunya virus (CHIKV) infection have not been thoroughly assessed using whole-body magnetic resonance imaging (WBMRI). This study aimed to determine the prevalence of these lesions in such patients. From September 2018 to February 2019, patients with positive Chikungunya-specific serology (Immunoglobulin M/Immunoglobulin G anti-CHIKV), with a history of polyarthralgia for > 6 months prior to MRI with no pre-existing rheumatic disorders, underwent 3T WBMRI and localized MRI. The evaluation focused on musculoskeletal inflammatory lesions correlated with chronic CHIKV infection. Pain levels were assessed using a visual analogue scale on the same day as WBMRI. The study included 86 patients of whom 26 met the inclusion criteria. All patients reported pain and most (92.3%) categorized it as moderate or severe. The most common finding across joints was effusion, particularly in the tibiotalar joint (57.7%) and bursitis, with the retrocalcaneal bursa most affected (48.0%). Tenosynovitis was prevalent in the flexor compartment of the hands (44.2%), while Kager fat pad and soleus edema were also observed. Bone marrow edema-like signals were frequently seen in the sacroiliac joints (19.2%). Most WBMRI findings were classified as mild. This study represents the first utilization of 3T WBMRI to assess musculoskeletal inflammatory disorders in chronic CHIKV infection. The aim was to identify the most affected joints and prevalent lesions, providing valuable insights for future research and clinical management of this condition regarding understanding disease pathophysiology, developing targeted treatment strategies, and using advanced imaging techniques in the assessment of musculoskeletal manifestations.

FHL1 promotes chikungunya and o’nyong-nyong virus infection and pathogenesis with implications for alphavirus vaccine design

Arthritogenic alphaviruses are positive-strand RNA viruses that cause debilitating musculoskeletal diseases affecting millions worldwide. A recent discovery identified the four-and-a-half-LIM domain protein 1 splice variant A (FHL1A) as a crucial host factor interacting with the hypervariable domain (HVD) of chikungunya virus (CHIKV) nonstructural protein 3 (nsP3). Here, we show that acute and chronic chikungunya disease in humans correlates with elevated levels of FHL1. We generated FHL1−/− mice, which when infected with CHIKV or o’nyong-nyong virus (ONNV) displayed reduced arthritis and myositis, fewer immune infiltrates, and reduced proinflammatory cytokine/chemokine outputs, compared to infected wild-type (WT) mice. Interestingly, disease signs were comparable in FHL1−/− and WT mice infected with arthritogenic alphaviruses Ross River virus (RRV) or Mayaro virus (MAYV). This aligns with pull-down assay data, which showed the ability of CHIKV and ONNV nsP3 to interact with FHL1, while RRV and MAYV nsP3s did not. We engineered a CHIKV mutant unable to bind FHL1 (CHIKV-ΔFHL1), which was avirulent in vivo. Following inoculation with CHIKV-ΔFHL1, mice were protected from disease upon challenge with CHIKV and ONNV, and viraemia was significantly reduced in RRV- and MAYV-challenged mice. Targeting FHL1-binding as an approach to vaccine design could lead to breakthroughs in mitigating alphaviral disease.

Incidence and factors associated with chronic chikungunya arthritis following chikungunya virus infection.

Chikungunya virus infection is a mosquito-borne illness. First-phase symptoms include fever, malaise, rash, and arthritis (self-limiting). Some patients can have chronic-phase symptoms, including chronic tenosynovitis, bursitis, and arthritis. This study aimed to determine the incidence and risk factors of chronic arthritis in patients with chikungunya infection. This retrospective cohort study analysed all adults diagnosed with chikungunya infection between 2015 and 2020 at our centre. Baseline and follow-up symptoms were evaluated in serologically confirmed cases. Chronic chikungunya arthritis was persistent arthritis >3 months after the onset. Patients who had preexisting chronic inflammatory arthritis and were lost to follow-up before 3 months from diagnosis were excluded. This study enrolled 120 patients. The median age was 51 (IQR 14) years, and 78% were female. The median number of joints with arthritis was 4 (IQR 8). The initial visual analog scale (VAS) score was 50 mm (IQR 40). Small joints of the hands, wrist, and knee (44.2%, 43.3%, and 42.3%, respectively) were the most affected. The incidence of chronic chikungunya arthritis was 40.4%. From the multivariable logistic regression, the initial number of joints with arthritis, initial VAS scores, and female sex were independently associated with chronic chikungunya arthritis with odds ratios of 1.09 (95% confidence interval [CI] 1.01-1.18), 1.03 (95% CI 1.01-1.06), and 4.17 (95% CI, 1.05-16.67), respectively. Chronic chikungunya arthritis is common in patients with chikungunya virus infection. Its predictive factors include the initial number of joints with arthritis, initial VAS scores, and female sex.

Pathogenesis of chronic chikungunya arthritis: Resemblances and links with rheumatoid arthritis.

Chikungunya virus (CHIKV) infection results from transmission by the mosquito vector. Following an incubation period of 5-7 days, patients develop an acute febrile illness, chikungunya fever (CHIKF), characterized by high fevers, maculopapular rash, headaches, polyarthritis/arthralgias, myalgias, nausea, vomiting, and diarrhea. Joint pain is often severe, and most often involves the hands, the wrists, the ankles, and the metatarsal-phalangeal joints of the feet. Many patients recover within several weeks, but up to 50% develop chronic joint pain and swelling for more than 12 weeks, then we refer to these symptoms as chronic chikungunya arthritis (CCA). The pathogenesis of CCA is not well understood. In this article, we suggest that mesenchymal stem cells (MSCs) may play an important role in this pathogenesis. This heterogeneous group of multipotent cells, morphologically similar to fibroblasts, may undergo epigenetic changes capable of generating aberrant progenies. However, we believe that there is no need for a latent infection. In our pathogenic hypothesis, CHIKV infection of MSCs would cause epigenetic changes both in MSCs themselves and in their progenies, without the need for reactivation of dormant viruses.

Symptomatic perception of patients affected by chronic chikungunya: a qualitative perspective

Objective: To understand the demands caused by chikungunya in the chronic phase and their impacts on patients’ mental health and quality of life. Materials and methods: This is a qualitative study, performed from November 2019 to January 2020. Focus groups and deep interviews were carried out. Then, the Discourse Analysis was performed. Results: Chronic pain was the main clinical manifestation reported by the participants, being responsible for affecting aspects related to quality of life and mental health. As for psycological view, this study showed that chronic pain was also reported as one of the main symptoms related to anxiety and depression among research subjects. Conclusion: this study demonstrated how the chronic illness caused by Chikungunya impacted the subjects' perception in the domains related to quality of life and mental health. Furthermore, we seek to focus on the management of disease in a holistic way, putting the patients’ own awareness of the impacts of the disease on their lives in a relevant level of their treatment.

Chikungunya in Brazil: An epidemic of high cost for private healthcare, 2017.

We evaluated the impact of direct and indirect medical costs incurred through chikungunya infections in patients treated in Fortaleza, Brazil. Cross-sectional study about the cost of illness. The valuation method of medical costs was based on the micro-costing approach (bottom-up). The study was carried out in a large general hospital of the private health network. The study population consisted of patients treated as suspected cases of chikungunya and hospital professionals who applied for sick leave due to chikungunya. In 2017, there were 2683 patients treated at this hospital who incurred an estimated cost of $383,514.40. From this amount, $174,322.91 (45.5%) were expended on emergency care, $194,700.59 (50.8%) on hospitalisations. 123 hospital professionals were infected with chikungunya and sick leave duration ranged between 1 and 19 days. Health professionals generated 746 days of absence and an amount of $14,490.90 due to absenteeism from work related to chikungunya. 31 symptoms were reported, especially arthralgia (91.1%) and fever (79.4%). There was a predominance of females (58.8%) and the age group of 20-39 years (42.1%). The average cost of admissions was over $2400. Considering the epidemic potential of chikungunya, our data indicate the huge economic burden of this disease to healthcare units in the presence of epidemics. Economic factors, added to the loss of life and the consequences of chronic chikungunya, make this disease a real scourge for countries with fewer material resources.

Determinants of Health-Related Quality of Life in Chronic Chikungunya Disease in Guadeloupe.

Chronic chikungunya disease is associated with a poor quality of life and a variety of symptoms, not restricted to the musculoskeletal system. Patients with chronic chikungunya disease in Guadeloupe were evaluated in order to identify the main factors determining the quality of life. Patients were followed up at a mean of 36 months after chikungunya infection, undergoing detailed clinical examination for musculoskeletal involvement, with assessment of subjective symptoms and the impact on mood, physical activity, and quality of life (SF12). Patients had extensive musculoskeletal involvement shown by tenderness in 9 ± 4 joints and stiffness in 5 ± 4 joints. SF12 physical and mental component scores showed a poor health-related quality of life. Measures of joint pain, stiffness, and inflammation contributed to impaired quality of life scores. In addition, fatigue and interrupted sleep appeared to be important predictors for physical aspects of quality of life. The emergence of anxiodepressive syndromes post-chikungunya infection was associated with both physical and mental component scores of SF12. These data confirm that musculoskeletal symptoms are not the only determinants of quality of life in chronic chikungunya disease. Follow-up of patients should include assessment and management of fatigue, poor sleep quality, and anxiodepressive syndromes.

Downregulation of CD73 on CD4+ T cells from patients with chronic Chikungunya infection

Chikungunya is an important mosquito-borne disease caused by the arthritogenic chikungunya virus, characterized by sporadic outbreaks all around the world. Although CD4+ T cells seem to have an important role in the pathogenesis of chikungunya, the mechanisms involved in this process are not yet fully elucidated. The ectoenzymes CD39 and CD73, also expressed by CD4 T lymphocytes, are involved in the hydrolysis of pro-inflammatory extracellular ATP and generation of immunosuppressive adenosine and seem to be modulated in some arthritogenic pathologies. However, their involvement in Chikungunya disease is unclear. Thus, using flow cytometry, we investigated peripheral CD4+ T cells from patients with acute and chronic chikungunya to assess the expression of ectonucleotidases CD39 and CD73 and coinhibitory receptors and production of cytokine and cytolytic granules. Patients in the acute phase displayed increased levels of PD-1, CTLA-4, IL-10, and IFN-γ compared to healthy individuals and patients in the chronic phase. Moreover, during chronic Chikungunya, analyses of Mean Fluorescent Intensity (MFI) demonstrated a reduced density of LAP, Perforin and Granzyme B compared to the healthy control. Finally, reduced levels of the ectoenzymes CD39 and CD73 expression was found during the chronic phase suggesting a possible modulation of extracellular ATP and adenosine by CD4+ T cells that may be involved in the persistence of arthritogenic symptoms.

Chronic Chikungunya arthralgia reduces functionality, quality of life and occupational performance: descriptive cross-sectional study

Chronic Chikungunya arthralgia reduces functionality, quality of life and occupational performance: descriptive cross-sectional study

Regulatory T cells in acute and chronic human Chikungunya infection

Chikungunya virus (CHIKV) infection generates strong immune responses that are associated with the disease pathophysiology. Regulatory T cells (Treg-cluster of differentiation (CD)-4+CD25highforkhead box P3 (FOXP3+)) are essential for the induction and maintenance of peripheral tolerance. Thus, they play key roles in determining the patient prognosis by preventing excessive immune responses via different suppression immune mechanisms. However, the regulatory mechanisms involved in human CHIKV infection are still poorly understood. Here, we characterize for the first time the Treg cell molecule-associated-mechanism during acute and chronic human Chikungunya disease. Here, we assessed the Treg cell population and molecule-associated mechanism in the peripheral blood samples of acute and chronic patients with Chikungunya. Our results indicate that CHIKV infection is associated with reduced frequency of Tregs, along with the impaired expression and production of Treg functional markers, including CD39, CD73, perforin, granzyme, programmed death 1 (PD-1), cytotoxic T lymphocyte antigen (CTLA)-4, and transforming growth factor (TGF)-β. This observation suggests that Treg cells possess the poor regulatory capacity in both acute and chronic phases of the disease. Taken together, these data provide significant evidence that the imbalanced response of Treg cells plays an essential role in establishing the pathogenesis of Chikungunya.

Tender and swollen joint counts are poorly associated with disability in chikungunya arthritis compared to rheumatoid arthritis

Chronic rheumatological manifestations similar to those of rheumatoid arthritis (RA) are described after chikungunya virus infection. We aimed to compare the relevance of joint counts and symptoms to clinical outcomes in RA and chronic chikungunya disease. Forty patients with chronic chikungunya arthralgia and 40 patients with RA were enrolled in a cross-sectional study. The association of tenderness and swelling, clinically assessed in 28 joints, and patient evaluations of pain and musculoskeletal stiffness with modified Health Assessment Questionnaire (HAQ) and quality of life (QoL) assessments were investigated. Tender and swollen joint counts, pain and stiffness scores were all associated with the HAQ disability index in RA (all r > 0.55, p ≤ 0.0002), but only stiffness was significantly associated with disability in chikungunya (r = 0.38, p = 0.02). Joint counts, pain and stiffness were also associated with most QoL domains in RA patients. In contrast, in chikungunya disease, tender joint counts were associated only with one QoL domain and swollen joints for none, while pain and stiffness were associated with several domains. Our results confirm the relevance of joint counts in RA, but suggest that in chronic chikungunya disease, joint counts have more limited value. Stiffness and pain score may be more important to quantify chikungunya arthritis impact.

Arthralgia resolution rate following chikungunya virus infection

BackgroundArthralgia, persistent pain or stiffness of the joints, is the hallmark symptom of chronic chikungunya virus (CHIKV) disease. Associated with significant disability and reduced quality of life, arthralgia can persist for many months following CHIKV infection. Understanding the expected duration of arthralgia persistence is important for managing clinical expectations at the individual-level as well as for estimating long-term burdens on population health following a CHIKV epidemic. MethodsA review of cohort studies reporting the prevalence of arthralgia post-CHIKV infection over multiple time points was conducted. Generalized linear models were used to estimate the average rate of arthralgia resolution following CHIKV infection. ResultsSixteen cohort studies matching the inclusion criteria were identified and included in the analysis. An average rate of arthralgia resolution of 10.85% (95% confidence interval (CI) 9.05–12.66%) per month was estimated across studies, corresponding to an expected median time to arthralgia resolution of 6.39 months (95% CI 5.48–7.66 months) and an expected arthralgia prevalence of 72.21% (95% CI 68.40–76.23%) at 3 months post-CHIKV infection. ConclusionsEstimates of the average rate of arthralgia resolution and the expected prevalence of arthralgia over time post-CHIKV infection were derived. These can help inform expectations regarding the long-term public health burdens associated with CHIKV epidemics.

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.