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

Abstract

Background: Arthritogenic 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 Re ´union 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 Findings: Patients 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/Significance: This 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.

Establishment and Comparison of Pathogenicity and Related Neurotropism in Two Age Groups of Immune Competent Mice, C57BL/6J Using an Indian Isolate of Chikungunya Virus (CHIKV)

“…Neuro-invasion by CHIKV causing viral encephalitis has also been observed, a rare complication recently reported observed mainly in the older patients [5,6,7]. In the post–pyretic or the post–acute phase, arthralgia continues leading to severe pain lasting for months till several years as reported by previous studies [8,9].…”

“…Several studies in patients >35 years of age, studying correlation between RF and age of patients have also reported similar outcomes of incapacitating arthritis during post–acute phase of CHIKV infection [52,53] and an overlap between RA and seropositive spondylarthritis [54] as observed in the older mice in this study. However, in younger adult age group, levels of RF were not necessarily elevated in the acute and chronic phases of the diseases, which may indicate inflammatory reaction induced arthritis emerged post–CHIKV infection [8].…”

Arthritogenic Alphaviruses: A Worldwide Emerging Threat?

“…This rate seems to depend on which CHIKV strain is involved [171]. In a recent prospective cohort of La Reunion Island patients [172], chronic joint pain concerned up to 83% of patients at 32 months and was accompanied by asthenia and depression [173]. As the virus has never been isolated from chronic swollen joints, it is thought that CHIKV acute infection might trigger host autoimmunity [172,174,175].…”

The Clinical Features, Pathogenesis and Methotrexate Therapy of Chronic Chikungunya Arthritis

“…In several studies, 25% to 62% of patients had arthritic symptoms 18 months after the onset of CHIKF [23,24]. Even at the 36-month follow-up, the prevalence of arthritis has been reported to be as high as 60% [12,13,25]. Among 152 Colombian patients evaluated at 26 weeks after disease onset, persistent arthritis was found in 54%, morning stiffness in 49%, joint edema in 41%, and both polyarthralgia and morning stiffness in 38% [26].…”

“…Similarly, Schilte et al [25] studied 180 patients with CHIKV arthritis of 36 months duration in whom the hands, wrists, ankles, and knees were most affected. Around 60%–80% of the patients had intermittent arthritis, while arthritis was unremitting in 20%–40%.…”