ORIGINAL ARTICLE Persistent Arthralgia and Related Risks Factors: A Cohort Study at 12 Months from Laboratory-Confirmed Chikungunya Infection Efr en Murillo-Zamora, a,b Oliver Mendoza-Cano, c,d Benjam  ın Trujillo-Hern andez, e Jos e Guzm an-Esquivel, e,f Enrique Higareda-Almaraz, g Martha Alicia Higareda-Almaraz, g Ram on Alberto S anchez-Pi~ na, d and Agustin Lugo-Radillo h a Departamento de Epidemiolog ıa, Unidad de Medicina Familiar No. 19, Instituto Mexicano del Seguro Social, Colima, Colima, M exico b Programa de Doctorado en Ciencias M edicas, Universidad de Colima, Facultad de Medicina, Colima, Colima, M exico c Facultad de Ingenier  ıa Civil, Universidad de Colima, Coquimatl an, Colima, M exico d T.H. Chan School of Public Health, Center for Health and the Global Environment, Harvard University, Boston, Massachusetts, USA e Facultad de Medicina, Universidad de Colima, Colima, Colima, M exico f Unidad de Investigaci on en Epidemiolog ıa Cl  ınica, Instituto Mexicano del Seguro Social, Colima, Colima, M exico g Jefatura de Servicios de Prestaciones M edicas, Instituto Mexicano del Seguro Social, Colima, Colima, M exico h CONACYT-Facultad de Medicina y Cirug ıa, Universidad Aut onoma Benito Ju arez de Oaxaca, Oaxaca, Oaxaca, M exico Received for publication May 30, 2017; accepted April 11, 2018 (ARCMED-D-17-00341). 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) 5 1.68; 95% confidence interval (CI), 1.10e2.55) and those with 8 or more arthralgia sites (RR 5 2.91, 95% CI 1.87e4.53) at acute disease had a significantly increased risk of PA at 12 months from CHIKV infec- tion. 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 man- ifestations (RR 5 7.06, 95% CI 2.97e16.81). Depressive symptoms (PHQ-2 score $3) were reported by 33.3% of PA-positive participants. Conclusions. Our findings suggest that chronic CHKV-related articular manifestations were a frequent event in the study sample and the impact on functional status was poten- tial. These results may be useful in health care settings in the risk-stratification of PA after CHIKV infection. Ó 2018 IMSS. Published by Elsevier Inc. Key Words: Chikungunya fever, Cohort studies, Risk, Arthralgia, Chronic pain, Mexico. Introduction Chikungunya virus (CHIKV), an arbovirus of the genus Alphavirus, is transmitted to humans through the bite of infected Aedes (Ae.) aegypti and Ae. albopictus mosquitoes (1). The virus is responsible for explosive outbreaks reported in most tropical and subtropical areas of the world Address reprint requests to: Oliver Mendoza-Cano, Dr., Center for Health and the Global Environment, T.H. Chan School of Public Health, Harvard University, 401 Park Drive, 4 th Floor West. Suite 415, PO Box 15677, Boston, MA 02215, USA; Phone: (þ1) (617) 384-8535; E-mail: oliver@ucol.mx or omendoza@hsph.harvard.edu 0188-4409/$ - see front matter. Copyright Ó 2018 IMSS. Published by Elsevier Inc. https://doi.org/10.1016/j.arcmed.2018.04.008 Archives of Medical Research - (2018) -