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

Antoine Bertolotti, Marême Thioune, Sylvie Abel, Gilda Belrose, Isabelle Calmont, Raymond Césaire, Minerva Cervantes, Laurence Fagour, Émilie Javelle, Catherine Lebris, Fatiha Najioullah, Sandrine Pierre-François, Benoît Rozé, Marie Vigan, Cédric Laouénan, André Cabié, Chronic Chikungunya working group of University Medical Center of Martinique, Antoine Bertolotti, Marême Thioune, Sylvie Abel, Gilda Belrose, Isabelle Calmont, Raymond Césaire, Minerva Cervantes, Laurence Fagour, Émilie Javelle, Catherine Lebris, Fatiha Najioullah, Sandrine Pierre-François, Benoît Rozé, Marie Vigan, Cédric Laouénan, André Cabié, Chronic Chikungunya working group of University Medical Center of Martinique

Abstract

Background: The chikungunya virus (CHIKV) is a re-emerging alphavirus that can cause chronic and potentially incapacitating rheumatic musculoskeletal disorders known as chronic chikungunya arthritis (CCA). We conducted a prospective cohort study of CHIKV-infected subjects during the 2013 chikungunya outbreak in Martinique. The aim of this study was to assess the prevalence of CCA at 12 months and to search for acute phase factors significantly associated with chronicity.

Methodology/principal findings: A total of 193 patients who tested positive for CHIKV RNA via qRT-PCR underwent clinical investigations in the acute phase (<21 days), and then 3, 6, and 12 months after inclusion. The Asian lineage was identified as the circulating genotype. A total of 167 participants were classified as either with or without CCA, and were analyzed using logistic regression models. The overall prevalence of CCA at 12 months was 52.1% (95%CI: 44.5-59.7). In univariate analysis, age (RD 9.62, 95% CI, 4.87;14.38, p<0.0001), female sex (RD 15.5, 95% CI, 1.03;30.0, p = 0.04), headache (RD 15.42, 95% CI, 0.65;30.18 p = 0.04), vertigo (RD 15.33, 95% CI, 1.47;29.19, p = 0.03), vomiting (RD 12.89, 95% CI, 1.54;24.24, p = 0.03), dyspnea (RD 13.53, 95% CI, 0.73;26.33, p = 0.04), intravenous rehydration (RD -16.12, 95% CI, -31.58; -0.66 p = 0.04) and urea (RD 0.66, 95% CI, 0.12;1.20, p = 0.02) were significantly associated with the development of CCA. For the subpopulation with data on joint involvement in the acute phase, the risk factors significantly associated with CCA were at least one 1 enthesitis (RD 16.7, 95%CI, 2.8; 30.7, p = 0.02) and at least one tenosynovitis (RD 16.8, 95% CI, 1.4-32.2, p = 0.04).

Conclusions: This cohort study conducted in Martinique confirms that CCA is a common complication of acute chikungunya disease. Our analysis emphasized the importance of age and female sex for CCA occurrence, and highlighted the aggravating role of dehydration during the acute phase. Early and adequate hydration were found to reduce the risk chronic chikungunya disorders.

Trial registration: clinicaltrials.gov (NCT01099852).

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Diagram of the study population.
Fig 1. Diagram of the study population.
“Unable”: patients unable to answer the question “Do you feel completely recovered from CHIKV-infection, in other words, are you now free of joint pain, rigidity, or edema related to this infection?”; “missed visit”: not present at a specific time point; “lost to follow-up”: patients who missed all follow-up visits from M3 onwards; “death”: dead patients; “CCA”: patients with chronic chikungunya arthritis; “no CCA”: patients without chronic chikungunya arthritis.
Fig 2. Loess curve between age and…
Fig 2. Loess curve between age and prevalence of chronic chikungunya according to sex.
Pink corresponds to female sex and blue to male sex. DAG-2 study 2014–2016, Martinique.

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