The Identification of Risk Factors for Chronic Chikungunya Arthralgia in Grenada, West Indies: A Cross-Sectional Cohort Study

Abstract

BackgroundChikungunya virus (CHIKV) is a re-emerging arboviral pathogen. In 2014, an explosive CHIKV outbreak occurred in Grenada, West Indies, infecting approximately 60% of the population. In approximately 50% of cases, CHIKV infection transitions to painful arthralgia that can persist for years. Elucidation of the risk factors for chronic disease is imperative to the development of effective risk management strategies and specific therapeutics.MethodsWe conducted a cross-sectional study of 240 people who were tested for CHIKV during the outbreak. We administered questionnaires to examine demographic, behavioral, psychological, social, and environmental factors to identify associations with chronic disease. Physical examinations were performed and persistent symptoms were recorded.ResultsEthnicity and socioeconomic status were not associated with risk of chronic joint pain. Female sex increased risk, and age was demonstrated to be predictive of chronic CHIKV sequelae. Mosquito avoidance behaviors did not reduce risk. Patients suffering joint pains, generalized body ache, and weakness in the extremities during acute infection were more likely to develop chronic arthralgia, and an increased duration of acute disease also increased risk.ConclusionsThese data demonstrate that chronic CHIKV affects people across the ethnic and socioeconomic spectrum, and it is not reduced by vector avoidance activity. Increased duration of acute symptoms, in particular acute joint pain, was strongly correlated with the risk of persistent arthralgia, thus effective clinical management of acute CHIKV disease could reduce burden of chronic CHIKV.

Occurrence of Chronic Stage Chikungunya in the General Population of Martinique during the First 2014 Epidemic: A Prospective Epidemiological Study

“…Only rare community-based prospective studies were found to be reported in the scientific literature concerning insular Caribbean populations. [36][37][38][39][40][41] In other world regions, past exploratory research on chronicity was conducted either prospectively on hospitalized and circumscribed patient samples or retrospectively amidst the general population. 5,[12][13][14] In light of the emerging public health burden of CHIK disease for the Caribbean region and the Americas, the present study aims mainly to provide a more comprehensive description of the epidemiological characteristics and health outcomes of chronic stage CHIK cases in the general population of Martinique.…”

“…Similar results were reported on Reunion Island and during other investigations. 12,14,20,[36][37][38]43,[47][48][49][50] These trends could be explained by the fact that a higher humoral immune response during acute CHIK infection phase could be associated with evolution toward chronic stage CHIK and persistent arthlagia. 51 Indeed, women, as compared with men, are known to have a stronger humoral immune system linked to female hormones.…”

“…best knowledge, the Martinique study is the only one to examine longitudinally such a large cohort of participants (N = 509), with a broad geographical assessment of the study population all over the island (recruiting GPs were located in different areas of the territory). [36][37][38][39][40][41] The approach to gathering late illness symptoms and QoL attributes (diverse range of physical and psychological health outcomes) has also been rarely conducted by other research teams. However, less than half of the eligible subjects identified by GPs finally participated in the follow-up phase, with 705 participants (58.1%) lost to follow-up between the initial recruitment and the followup phases.…”

Prevalence of chronic chikungunya and associated risks factors in the French West Indies (La Martinique): A prospective cohort study

“…During previous outbreaks, age over 50 and female sex were shown to be the main risk factors for chronic chikungunya disease [6,32,34,40,41,48,49]. Some studies focusing on gender have suggested that the menstrual cycle [50] and ovulation influence the production of proinflammatory cytokines by monocytes [50,51] and that estradiol plays a role in the increase of antibody production [52,53].…”

The Chikungunya virus nsP3 macro domain inhibits activation of the NF-κB pathway

“…Infection with CHIKV causes Chikungunya fever, characterised by high fever, rash and joint pain which can be debilitating and, in some cases, persistent 3 . CHIKV infection induces a highly inflammatory state, inducing tissue damage 4 .…”