Predictors of Chikungunya rheumatism: a prognostic survey ancillary to the TELECHIK cohort study

Patrick Gérardin, Adrian Fianu, Alain Michault, Corinne Mussard, Karim Boussaïd, Olivier Rollot, Philippe Grivard, Somar Kassab, Eric Bouquillard, Gianandrea Borgherini, Bernard-Alex Gaüzère, Denis Malvy, Gérard Bréart, François Favier, Patrick Gérardin, Adrian Fianu, Alain Michault, Corinne Mussard, Karim Boussaïd, Olivier Rollot, Philippe Grivard, Somar Kassab, Eric Bouquillard, Gianandrea Borgherini, Bernard-Alex Gaüzère, Denis Malvy, Gérard Bréart, François Favier

Abstract

Introduction: Long-lasting relapsing or lingering rheumatic musculoskeletal pain (RMSP) is the hallmark of Chikungunya virus (CHIKV) rheumatism (CHIK-R). Little is known on their prognostic factors. The aim of this prognostic study was to search the determinants of lingering or relapsing RMSP indicative of CHIK-R.

Methods: Three hundred and forty-six infected adults (age≥15 years) having declared RMSP at disease onset were extracted from the TELECHIK cohort study, Reunion island, and analyzed using a multinomial logistic regression model. We also searched for the predictors of CHIKV-specific IgG titres, assessed at the time of a serosurvey, using multiple linear regression analysis.

Results: Of these, 111 (32.1%) reported relapsing RMSP, 150 (43.3%) lingering RMSP, and 85 (24.6%) had fully recovered (reference group) on average two years after acute infection. In the final model controlling for gender, the determinants of relapsing RMSP were the age 45-59 years (adjusted OR: 2.9, 95% CI: 1.0, 8.6) or greater or equal than 60 years (adjusted OR: 10.4, 95% CI: 3.5, 31.1), severe rheumatic involvement (fever, at least six joints plus four other symptoms) at presentation (adjusted OR: 3.6, 95% CI: 1.5, 8.2), and CHIKV-specific IgG titres (adjusted OR: 3.2, 95% CI: 1.8, 5.5, per one unit increase). Prognostic factors for lingering RMSP were age 45-59 years (adjusted OR: 6.4, 95% CI: 1.8, 22.1) or greater or equal than 60 years (adjusted OR: 22.3, 95% CI: 6.3, 78.1), severe initial rheumatic involvement (adjusted OR: 5.5, 95% CI: 2.2, 13.8) and CHIKV-specific IgG titres (adjusted OR: 6.2, 95% CI: 2.8, 13.2, per one unit increase). CHIKV specific IgG titres were positively correlated with age, female gender and the severity of initial rheumatic symptoms.

Conclusions: Our data support the roles of age, severity at presentation and CHIKV specific IgG titres for predicting CHIK-R. By identifying the prognostic value of the humoral immune response of the host, this work also suggest a significant contribution of the adaptive immune response to the physiopathology of CHIK-R and should help to reconsider the paradigm of this chronic infection primarily shifted towards the involvement of the innate immune response.

Figures

Figure 1
Figure 1
Prognostic survey participation profile. RMSP, rheumatic musculoskeletal pain. The prognostic survey cohort sample was issued from the TELECHIK survey, a population-based cohort study (November 2007 to May 2008) (23). After elimination of 582 Chikungunya virus (CHIKV)-seronegative subjects and 90 subjects not presenting with RMSP at disease onset, 76 subjects were excluded (50 children, 15 adults for relocations and absence of contact, 11 for the absence of overt temporality in the clinical course of Chikungunya rheumatism), leaving 346 eligible adult participants assessed on the course of RMSP. This population was shifted towards the selection of more women and older participants.
Figure 2
Figure 2
Stratification of Chikungunya virus (CHIKV)-specific IgG titre levels according to explanatory variables in the TELECHIK study, La Réunion, 2007 to 2008. (CHIKV)-specific IgG titre levels are shown by gender in the two age groups (A), by age in according to gender (B), by severity of presentation in the two age groups (C), and by severity of presentation by age group and gender (D). Boxes represent medians and interquartile (Q1-Q3) ranges, whiskers represent minimal and maximal values. Optic density values were compared using Mann-Whitney tests: *P < 0.05; **P < 0.01; ***P < 0.001.

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