Risk of chronic arthralgia and impact of pain on daily activities in a cohort of patients with chikungunya virus infection from Brazil

Silva, Monaíse M. O.; Kikuti, Mariana; Anjos, Rosângela O.; Portilho, Moyra Machado; Santos, Viviane Cristina Fernandes dos; Gonçalves, T. S.; Tauro, Laura B.; Moreira, Patrícia S.S.; Jacob-Nascimento, Leile Camila; Santana, Perla M.; Campos, Gúbio Soares; Siqueira, André Machado; Kitron, Uriel; Reis, Mitermayer Galvão dos; Ribeiro, Guilherme S.

doi:10.1016/j.ijid.2021.03.003

Cited by 9 publications

(12 citation statements)

References 47 publications

(58 reference statements)

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“…As already found in other studies [29,32], in our cohort the univariate analysis shows that females had worse prognosis. Although some studies have found that age can be determining factor for chronification [12,38], in our population this finding could not be reproduced.…”

Section: Plos Neglected Tropical Diseasessupporting

confidence: 90%

Clinical markers of post-Chikungunya chronic inflammatory joint disease: A Brazilian cohort

et al. 2023

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Background Chikungunya-fever (CHIKF) remains a public health major issue. It is clinically divided into three phases: acute, post-acute and chronic. Chronic cases correspond to 25–40% individuals and, though most of them are characterized by long-lasting arthralgia alone, many of them exhibit persistent or recurrent inflammatory signs that define post-Chikungunya chronic inflammatory joint disease (pCHIKV-CIJD). We aimed to identify early clinical markers of evolution to pCHIKV-CIJD during acute and post-acute phases. Methodology/Principal findings We studied a prospective cohort of CHIKF-confirmed volunteers with longitudinal clinical data collection from symptoms onset up to 90 days, including a 21-day visit (D21). Of 169 patients with CHIKF, 86 (50.9%) completed the follow-up, from whom 39 met clinical criteria for pCHIKV-CIJD (45.3%). The relative risk of chronification was higher in women compared to men (RR = 1.52; 95% CI = 1.15–1.99; FDR = 0.03). None of the symptoms or signs presented at D0 behaved as an early predictor of pCHIKV-CIJD, while being symptomatic at D21 was a risk factor for chronification (RR = 1.31; 95% CI = 1.09–1.55; FDR = 0.03). Significance was also observed for joint pain (RR = 1.35; 95% CI = 1.12–1.61; FDR = 0.02), reported edema (RR = 3.61; 95% CI = 1.44–9.06; FDR = 0.03), reported hand and/or feet small joints edema (RR = 4.22; 95% CI = 1.51–11.78; FDR = 0.02), and peri-articular edema observed during physical examination (RR = 2.89; 95% CI = 1.58–5.28; FDR = 0.002). Furthermore, patients with no findings in physical examination at D21 were at lower risk of chronic evolution (RR = 0.41, 95% CI = 0.24–0.70, FDR = 0.01). Twenty-nine pCHIKV-CIJD patients had abnormal articular ultrasonography (90.6% of the examined). The most common indings were synovitis (65.5%) and joint effusion (58.6%). Conclusion This cohort has provided important insights into the prognostic evaluation of CHIKF. Symptomatic sub-acute disease is a relevant predictor of evolution to chronic arthritis with synovitis, drawing attention to joint pain, edema, multiple articular involvement including small hand and feet joints as risk factors for chronification beyond three months, especially in women. Future studies are needed to accomplish the identification of accurate and early biomarkers of poor clinical prognosis, which would allow better understanding of the disease’s evolution and improve patients’ management, modifying CHIKF burden on global public health.

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Section: Plos Neglected Tropical Diseasessupporting

confidence: 90%

Clinical markers of post-Chikungunya chronic inflammatory joint disease: A Brazilian cohort

et al. 2023

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“…We had previously reported that 42.5% of the 153 chikungunya patients detected during our surveillance for acute febrile illness that were followed by telephone calls developed chronic arthralgia that lasted >3 months (10). In this subsample of 146 chikungunya patients that were followed and had available sera for cytokine and chemokine testing, the frequency of chronic arthralgia was exactly the same (42.5%).…”

Section: Discussionmentioning

confidence: 52%

“…Acutephase (≤7 days after symptoms onset) and convalescent-phase (15-40 days after symptoms onset) blood samples were collected, centrifuged and sera were frozen at -80°C and -20°C until molecular and serological analyses, respectively. Between November 2016 and March 2017, telephone follow-up was performed for all patients who had laboratory evidence of CHIKV infection to obtain self-reported data on disease resolution or progression and on duration of arthralgia (10).…”

Section: Patients and Study Designmentioning

confidence: 99%

“…Although most of the patients have a self-limited disease course, some individuals can progress to a chronic phase, characterized by continuous of recurring polyarthralgia that may last from months to years (7). Chronic arthralgia post-CHIKV infection also can lead to limitation of movements, incapacity for work, and even depression, directly affecting household incomes and representing a significant disease burden for affected populations (8)(9)(10). Therefore, it is necessary to elucidate the mechanisms that lead to chronic articular pain in some patients with chikungunya in order to prevent this complication.…”

Section: Introductionmentioning

confidence: 99%

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Acute-Phase Levels of CXCL8 as Risk Factor for Chronic Arthralgia Following Chikungunya Virus Infection

et al. 2021

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The immunopathogenesis of chikungunya virus (CHIKV) infection and the role of acute-phase immune response on joint pain persistence is not fully understood. We investigated the profile of serum chemokine and cytokine in CHIKV-infected patients with acute disease, compared the levels of these biomarkers to those of patients with other acute febrile diseases (OAFD) and healthy controls (HC), and evaluated their role as predictors of chronic arthralgia development. Chemokines and cytokines were measured by flow Cytometric Bead Array. Patients with CHIKV infection were further categorized according to duration of arthralgia (≤ 3 months vs >3 months), presence of anti-CHIKV IgM at acute-phase sample, and number of days of symptoms at sample collection (1 vs 2-3 vs ≥4). Patients with acute CHIKV infection had significantly higher levels of CXCL8, CCL2, CXCL9, CCL5, CXCL10, IL-1β, IL-6, IL-12, and IL-10 as compared to HC. CCL2, CCL5, and CXCL10 levels were also significantly higher in patients with CHIKV infection compared to patients with OAFD. Patients whose arthralgia lasted > 3 months had increased CXCL8 levels compared to patients whose arthralgia did not (p<0.05). Multivariable analyses further indicated that high levels of CXCL8 and female sex were associated with arthralgia lasting >3 months. Patients with chikungunya and OAFD had similar cytokine kinetics for IL-1β, IL-12, TNF, IFN-γ, IL-2, and IL-4, although the levels were lower for CHIKV patients. This study suggests that chemokines may have an important role in the immunopathogenesis of chronic chikungunya-related arthralgia.

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“…Chikungunya virus (CHIKV) is a mosquito-borne virus that causes fever, rashes, and joint pain in infected patients. During acute infection, joint pain can be very severe; importantly, a subset of those infected (up to 40% in some outbreaks) experience debilitating chronic joint pain for months, sometimes up to years [1][2][3][4]. First described in Tanzania in 1952, the virus is currently endemic in countries in Africa, and Asia; since 2007, there have been reports of autochthonous infections in Europe and in 2013, the Americas [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

A Novel Sphingosine Kinase Inhibitor Suppresses Chikungunya Virus Infection

Oyewole

Dunnavant

Bhattarai

et al. 2022

Viruses

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Chikungunya virus (CHIKV) is a re-emerging arbovirus in the alphavirus genus. Upon infection, it can cause severe joint pain that can last years in some patients, significantly affecting their quality of life. Currently, there are no vaccines or anti-viral therapies available against CHIKV. Its spread to the Americas from the eastern continents has substantially increased the count of the infected by millions. Thus, there is an urgent need to identify therapeutic targets for CHIKV treatment. A potential point of intervention is the sphingosine-1-phosphate (S1P) pathway. Conversion of sphingosine to S1P is catalyzed by Sphingosine kinases (SKs), which we previously showed to be crucial pro-viral host factor during CHIKV infection. In this study, we screened inhibitors of SKs and identified a novel potent inhibitor of CHIKV infection—SLL3071511. We showed that the pre-treatment of cells with SLL3071511 in vitro effectively inhibited CHIKV infection with an EC50 value of 2.91 µM under both prophylactic and therapeutic modes, significantly decreasing the viral gene expression and release of viral particles. Our studies suggest that targeting SKs is a viable approach for controlling CHIKV replication.

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Risk of chronic arthralgia and impact of pain on daily activities in a cohort of patients with chikungunya virus infection from Brazil

Cited by 9 publications

References 47 publications

Clinical markers of post-Chikungunya chronic inflammatory joint disease: A Brazilian cohort

Clinical markers of post-Chikungunya chronic inflammatory joint disease: A Brazilian cohort

Acute-Phase Levels of CXCL8 as Risk Factor for Chronic Arthralgia Following Chikungunya Virus Infection

A Novel Sphingosine Kinase Inhibitor Suppresses Chikungunya Virus Infection

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