Original Article
Epidemiological
Persistent Arthralgia and Related Risks Factors: A Cohort Study at 12 Months from Laboratory-Confirmed Chikungunya Infection

https://doi.org/10.1016/j.arcmed.2018.04.008Get rights and content

Aim of the study

To assess the cumulative incidence and clinical markers associated with persistent arthralgia (PA) at 12 months from acute chikungunya virus (CHIKV) infection.

Methods

A multicenter retrospective cohort study was conducted in the state of Colima, Mexico, and 217 serologically confirmed cases of CHIKV infection were enrolled. Participants aged 15 years and older were interviewed on 6 months basis from acute illness onset and the main binary outcome was self-reported PA at 12 months. To assess clinical markers associated with PA we used a generalized linear model. The 2-item Patient Health Questionnaire (PHQ-2) was used to screen for depressive symptoms among PA-positive individuals.

Results

The cumulative incidence of PA was 31.8%. In the generalized linear model, individuals ≥40 years of age (risk ratio (RR) = 1.68; 95% confidence interval (CI), 1.10–2.55) and those with 8 or more arthralgia sites (RR = 2.91, 95% CI 1.87–4.53) at acute disease had a significantly increased risk of PA at 12 months from CHIKV infection. Self-reported arthralgia (any site) at 3 months post-infection, a sub-chronic clinical marker, was also associated with a significantly increased risk of long-term articular manifestations (RR = 7.06, 95% CI 2.97–16.81). Depressive symptoms (PHQ-2 score ≥3) were reported by 33.3% of PA-positive participants.

Conclusions

Our findings suggest that chronic CHKV-related articular manifestations were a frequent event in the study sample and the impact on functional status was potential. These results may be useful in health care settings in the risk-stratification of PA after CHIKV infection.

Introduction

Chikungunya virus (CHIKV), an arbovirus of the genus Alphavirus, is transmitted to humans through the bite of infected Aedes (Ae.) aegypti and Ae. albopictus mosquitoes (1). The virus is responsible for explosive outbreaks reported in most tropical and subtropical areas of the world 2, 3, 4. Due to the fact that there is no effective vaccine or specific pharmacological treatment, the CHIKV represents a major global challenge for health systems 5, 6.

In Mexico, the first autochthonous case of CHIKV infection was reported in the last trimester of 2014 in the state of Chiapas, located in the southeastern region of the country (7). Several disease outbreaks were then reported nationally in most of the areas where the arthropod vectors are found. The CHIKV was isolated in nearly 80% of blood samples from febrile patients between 2014 and 2015 (Chiapas, Mexico) (8).

The state of Colima (pop 711,200 inhabitants) is located in the western part of the country and the permanent presence of Ae. aegypti has been documented 9, 10. Public medical units of the Mexican Institute of Social Security (from the Spanish Instituto Mexicano del Seguro Social, IMSS) registered nearly 7,500 cases of CHIKV infection within the time frame of March 2015 (when the first autochthonous case was identified) and December 2016. The unadjusted incidence rates were 2,083 and 132 cases per 100,000 affiliated in 2015 and 2016 respectively (Figure 1).

Acute infection is symptomatic in more than 75% of infected individuals and it is characterized by abrupt peripheral arthralgia and impaired ambulation (11). It is frequently self-limited and resolves within 7–10 d, but a subset of patients experience persisting arthralgia (PA) lasting from months to years (12). The current scientific knowledge regarding the factors associated with increased risk of PA is limited and the impact on the functional status of the patient is potential (13). Most of the published studies have been conducted in the Réunion Island, in the Indian Ocean 14, 15, 16, 17, 18, and ethnic differences in chronic pain perception are plausible (19).

The present study aimed to estimate the cumulative incidence of PA at 12 months from acute laboratory-confirmed CHIKV infection among adults and to evaluate the association of several clinical markers with the risk of chronic articular manifestations. In addition, we screened for depressive symptoms among PA-positive individuals.

Section snippets

Study Design

A multicenter retrospective cohort study was conducted in the state of Colima, Mexico, from December 2015–January 2017. The database from the National System for Epidemiological Surveillance (from the Spanish Sistema Nacional de Vigilancia Epidemiológica, SINAVE) was used to identify the eligible individuals. The SINAVE uses a web-based platform to report suspected cases identified at public and private health facilities according to governmental standards (20). The study was conducted at

Results

Data from the 217 laboratory-confirmed cases of CHIKV infection were analyzed and the study profile is shown in Figure 2. No deaths were registered during the follow-up. The cumulative incidence of PA at 6 months post-infection was 42.9%, which is similar to the frequency observed in a previously published analysis on a subsample of individuals (41.9%, p = 0.054) (21). The mean interval between acute illness onset and the date of the interview was 368.3 ± 7.7 natural days. Table 1 shows the

Discussion

Our findings suggest that nearly one third (31.8%) of adults with laboratory-confirmed CHIKV infection persist with articular pain at 12 months from the acute illness. We also found that three clinical markers (age of 40 years or older, 8 or more arthralgia sites at acute disease and self-reported pain at 3 months post-infection) were associated with a significantly increased risk of chronic articular manifestations.

The impact of the CHIKV-associated PA on functional status was potential, since

Conclusions

In the study population, the long-term articular manifestations of CHIKV infection appear to be a frequent event. Three clinical markers were associated with an increased risk of PA at 12 months from acute illness: age (≥40 years), total number of sites of arthralgia (≥8 painful sites) and self-reported arthralgia at 3 months post-infection. These factors may be useful in healthcare settings for the opportune identification of patients in whom an early and specialized medical intervention would

Acknowledgments

The researchers would like to thank to all the practicing physicians of family medicine that participated in the data collection.

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