Long-term Arthralgia Research Articles

A clinical scoring system to predict long-term arthralgia in Chikungunya disease: Acohort study.

BackgroundChikungunya virus (CHIKV) has caused worldwide epidemics that impose a major burden on health systems. Approximately half of infected individuals develop chronic debilitating arthralgia, affecting their quality of life. Here, we identified the relevant clinical and demographic variables in the acute phase of CHIKV infection prospectively linked to chronic arthralgia to elaborate a prognostic scoring system.MethodsAcute CHIKV infection cases (n = 134) confirmed by serology or molecular test were examined <10 days of disease onset and followed for one year to evaluate for disease progression. Potential risk factors for chronic arthralgia were evaluated by multivariate analysis to develop a prognostic scoring system, which was subsequently tested in an independent validation cohort consisting of 42 individuals.ResultsA total of 107 out of 134 (80%) acute CHIKV-confirmed cases from the derivation cohort were re-examined one year after enrollment. Chronic arthralgia post-CHIKV infection was diagnosed in 64 (60%). Five of the 12 parameters evaluated in the acute phase were statistically associated with persistent arthralgia and were further tested by Bayesian analysis. These variables were weighted to yield a prognosis score denominated SHERA (Sex, Hypertension, Edema, Retroocular pain, Age), which exhibited 81.3% accuracy in predicting long-term arthralgia post-CHIKV infection in the derivation cohort, and 76.5% accuracy in the validation cohort.ConclusionsThe simplified and externally validated prognostic scoring system, SHERA, is a useful method to screen acutely CHIKV-infected patients at elevated risk of chronic arthralgia who will benefit from specific interventions. This tool could guide public health policies, particularly in resource-constrained settings.

Description and Validation of a Clinical Scoring System to Predict Chronic Arthralgia in Chikungunya Disease

Background: The emergence of the Chikungunya virus (CHIKV) has resulted in worldwide epidemics that impose a major burden on health systems. Infection is often characterized by chronic debilitating arthralgia in approximately half of infected individuals, resulting in long-term effects on patients' quality of life. The early identification of affected individuals at risk of chronic implications may help direct efforts to attenuate the physical and emotional impact of infection, thereby reducing the socio-economic impact of outbreaks. Some predictive markers of chronic disease risk have been identified, yet their application is limited in clinical settings. Here, we prospectively identified the relevant clinical and demographic variables in the acute phase of Chikungunya infection that were linked to the persistence of arthralgia one year later in an attempt to elaborate a prognostic scoring system. Methods: Individuals with acute CHIKV infection (n=133), confirmed by serology or molecular test, were examined <10 days of disease onset and followed for one year to determine disease progression. Potential risk factors for chronic arthralgia were evaluated by multivariate analysis to develop a prognostic scoring system, which was subsequently tested in an independent validation cohort consisting of 45 individuals. Findings: A total of 106 acute CHIKV-confirmed cases from the derivation cohort were re-examined one year after enrollment. Chronic arthralgia post-CHIKV infection was diagnosed in 61 out of the 106 (68%) re-examined patients. Five out of the 13 clinical and sociodemographic parameters evaluated in the acute phase were found to be statistically associated with persistent arthralgia by univariate analysis. These variables were tested by Bayesian analysis to explore the complex relationships of the multiple variables on disease outcome, and then weighted to elaborate a composite score denominated SHERA (Sex, Hypertension, Edema, Retroocular pain, Age) to discriminate between individuals at low or high risk of chronic arthralgia. The SHERA scoring system presented 81·1% accuracy in predicting long-term arthralgia post-CHIKV infection in the derivation cohort, and 86·8% accuracy in the independent validation cohort. Interpretation: The presently developed simplified and externally validated prognostic scoring system could prove useful in screening acute CHIKV-infected patients who face an elevated risk of developing chronic arthralgia manifestations, and who may benefit from specific interventions in the initial phase of infection. The early identification of high-risk individuals could guide public health policies, particularly in resource-constrained settings. Funding Statement: This work was supported by CNPq (439967/2016-3), PROEP (420765/2017-4) and FINEP (MCTIC/FINEP/FNDCT 01/2016 ZIKA - 0416006000). AB and MB-N are CNPq fellows. Declaration of Interests: The authors declare none. Ethics Approval Statement: This study was approved by the Institutional Review Board of the School of Medicine - Federal University of Bahia (approval numbers: derivation cohort – 1·657·324; validation cohort – 1·450·762).

Laboratory Diagnostic Options and Challenges for Chikungunya Viruses

Background: Chikungunya infection is a Aedes mosquito transmitted viral disease caused by Chikungunya virus (CHIKV), a member of the Alphavirus genus. It is an important human pathogen that causes a syndrome characterized by fever, chills, headache and severe joint pain usually of the smaller joints, with or without swelling. Though the disease is almost self-limiting, during the recent outbreak CHIKV was also found to cause long-term arthralgia, neurological disease and even few fatalities. Despite the fact that CHIKV is associated with epidemics of unprecedented magnitude, only a few specific serological and molecular diagnostic tools are available.Objective: CHIKV diagnosis is essentially based on virus isolation, reverse transcription (RT)-PCR and ELISA assays. The gold standard of CHIKV diagnosis is culture, however, required facilities and skills are not available in any routine laboratory in the country. Highly sensitive and specific PCR assays for CHIKV have been developed and commercially available.Conclusion: Although the reagents and equipment are costly for widespread use RT-PCR is the method of choice for the early detection and confirmation of virus in clinical samples as most acutely infected patients seek medical attention within the first few days of illness when role of serology based diagnosis is minimum.Pulse Vol.10 January-December 2017 p.18-24

Long-term Chikungunya Sequelae in Curaçao: Burden, Determinants, and a Novel Classification Tool.

Beyond the acute illness phase, chikungunya constitutes a public health problem given its chronic disease phase, which may include long-term arthralgia, arthritis, fatigue, and depression. Currently, there is no consensus on how to define chikungunya chronicity. A comprehensive cross-sectional survey was performed in Curaçao in June and July 2015 to evaluate 304 adult laboratory-confirmed chikungunya patients 3-16 months after diagnosis. We developed a novel tool, the Curaçao Long-Term Chikungunya Sequelae (CLTCS) score, to classify chronic chikungunya disease and estimate its burden regarding disease duration, clinical presentation, and impact on quality of life. Disease persistence was estimated to be 79% one month after symptom onset and 64% after 400 days. Chikungunya persistence was characterized by higher proportions of arthralgia, weakness, myalgia, and age 41-60 years. Individuals were classified as "highly affected," "mildly affected," and "recovered." "Highly affected" disease status was associated with clinical complaints (arthralgia, weakness, loss of vitality, and being diabetic) and major decreases in quality-of-life scores. In the Caribbean, a high proportion of chikungunya patients remains chronically affected. We propose the CLTCS as a suitable score to easily and rapidly classify the severity of chikungunya chronic disease and to assess the need for symptom-alleviating treatment.

Persistent arthralgia and related risks factors in laboratory-confirmed cases of Chikungunya virus infection in Mexico

ABSTRACTObjective.To estimate the cumulative incidence of persistent arthralgia at 6 months from acute Chikungunya virus (CHIKV) infection and to evaluate the association of clinical markers with the risk of long-term arthralgia.Methods.This multicenter retrospective cohort study was conducted in the Mexican state of Colima. A total of 136 individuals aged 15 years and older with serologically confirmed CHIKV infection were enrolled. Participants were interviewed at 6 months from the onset of symptoms, and self-reported persistent arthralgia (PA) was the main binary outcome. A self-report numeric rating scale (NRS) ranging from 0 to 10 was used to estimate the severity of articular pain.Results.The cumulative incidence of PA was 41.9%. Severe pain (NRS ≥ 7) presented in 36.8% of participants with PA. In multiple analysis, individuals aged 40 years and older (risk ratio (RR) = 1.60; 95% confidence interval (CI), 1.03-2.48) and those with articular pain at 3 months post-infection (RR = 3.95; 95% CI, 1.95-8.01) had a significantly increased risk of PA at 6 months from CHIKV infection.Conclusions.To the best of our knowledge, this is first report of a CHIKV-associated longterm outcome in Mexico, where the incidence of the infection has been high. This is also the first study in Latin America evaluating several factors associated with the risk of PA. Our findings may be useful in health care settings to stratify the risk of chronic arthralgia secondary to CHIKV infection and to identify patients who would benefit clinically from early medical intervention.

Long-Term Arthralgia after Mayaro Virus Infection Correlates with Sustained Pro-inflammatory Cytokine Response.

Mayaro virus (MAYV), an alphavirus similar to chikungunya virus (CHIKV), causes an acute debilitating disease which results in the development of long-term arthralgia in more than 50% of infected individuals. Currently, the immune response and its role in the development of MAYV-induced persistent arthralgia remain unknown. In this study, we evaluated the immune response of individuals with confirmed MAYV infection in a one-year longitudinal study carried out in Loreto, Peru. We report that MAYV infection elicits robust immune responses that result in the development of a strong neutralizing antibody response and the secretion of pro-inflammatory immune mediators. The composition of these inflammatory mediators, in some cases, differed to those previously observed for CHIKV. Key mediators such as IL-13, IL-7 and VEGF were strongly induced following MAYV infection and were significantly increased in subjects that eventually developed persistent arthralgia. Although a strong neutralizing antibody response was observed in all subjects, it was not sufficient to prevent the long-term outcomes of MAYV infection. This study provides initial immunologic insight that may eventually contribute to prognostic tools and therapeutic treatments against this emerging pathogen.

Mayaro Virus Infection, Amazon Basin Region, Peru, 2010–2013

During 2010–2013, we recruited 16 persons with confirmed Mayaro virus infection in the Peruvian Amazon to prospectively follow clinical symptoms and serologic response over a 12-month period. Mayaro virus infection caused long-term arthralgia in more than half, similar to reports of other arthritogenic alphaviruses.

Chikungunya Virus-associated Long-term Arthralgia: A 36-month Prospective Longitudinal Study

BackgroundArthritogenic alphaviruses, including Chikungunya virus (CHIKV), are responsible for acute fever and arthralgia, but can also lead to chronic symptoms. In 2006, a Chikungunya outbreak occurred in La Réunion Island, during which we constituted a prospective cohort of viremic patients (n = 180) and defined the clinical and biological features of acute infection. Individuals were followed as part of a longitudinal study to investigate in details the long-term outcome of Chikungunya.Methodology/Principal FindingsPatients were submitted to clinical investigations 4, 6, 14 and 36 months after presentation with acute CHIKV infection. At 36 months, 22 patients with arthralgia and 20 patients without arthralgia were randomly selected from the cohort and consented for blood sampling. During the 3 years following acute infection, 60% of patients had experienced symptoms of arthralgia, with most reporting episodic relapse and recovery periods. Long-term arthralgias were typically polyarthralgia (70%), that were usually symmetrical (90%) and highly incapacitating (77%). They were often associated with local swelling (63%), asthenia (77%) or depression (56%). The age over 35 years and the presence of arthralgia 4 months after the disease onset are risk factors of long-term arthralgia. Patients with long-term arthralgia did not display biological markers typically found in autoimmune or rheumatoid diseases. These data helped define the features of CHIKV-associated chronic arthralgia and permitted an estimation of the economic burden associated with arthralgia.Conclusions/SignificanceThis study demonstrates that chronic arthralgia is a frequent complication of acute Chikungunya disease and suggests that it results from a local rather than systemic inflammation.

Laboratory diagnosis of chikungunya virus: Do we really need it?

Chikungunya (CHIK) fever is a re-emerging Aedes mosquito-transmitted viral disease caused by CHIK virus belonging to the Togaviridae family of genus Alphavirus. The disease is almost self-limiting, occurs with characteristic triad of sudden onset fever, rash and arthritis. During the recent outbreak CHIKV was also found to cause long-term arthralgia, severe neurological disease and even fatalities. Although there are no antiviral or vaccines available for CHIKV, still there are several advantages to diagnose the infection. The present article provides an overview of various diagnostic modalities available and its significance by searching PubMed MeSH terms "Chikungunya virus" and "Diagnosis" for recent articles. The gold standard of CHIKV diagnosis is culture, yet requires facilities and skills. Highly sensitive and specific PCR assays for CHIKV have been developed, but the reagents and equipment are costly for widespread use. Serological diagnosis by detecting IgM antibody is most widely used as it is relatively cheaper and easier to perform. Disadvantages of antibody testing are cross-reactivity with other alpha viruses, cannot differentiate between recent past and acute infection, and its sensitivity varies in clinical settings. When tested for diagnosing acute CHIKV disease, sensitivities were just 4 to 22% and after 1 week rose to more than 80%. As most acutely infected patients seek medical attention within the first few days of illness, the ideal test should detect RNA or antigen. Therefore, the more realistic aim would be to develop a reliable antigen detection assay that could be used in rural areas, where CHIKV infection often occurs.