Marc Lecuit, Florence Carpentier, Thérèse Couderc, Clémentine Schilte, Yoann Madec, Somar Kassab, Alain Michault, Matthew L. Albert, Frédérik Staikovsky, Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Emergency Department, Pôle des Spécialités de l'Urgence, Centre Hospitalier Régional de La Réunion (CHR Réunion), Biologie des Infections - Biology of Infection, Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), BIOlogie et GEstion des Risques en agriculture (BIOGER), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Microorganismes et Barrières de l'Hôte (Equipe avenir), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), This study was funded by the CRVOI (Centre de Recherche et de Veille sur les maladies émergentes dans l’Océan Indien), Institut Pasteur, Inserm (Institut National de la Santé et de la Recherche Médicale), Labex IBEID, Fondation pour la Recherche Médicale, BNP-Paribas Foundation and Mairie de Paris, ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ProdInra, Archive Ouverte, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Microbiologie Fondamentale et Pathogénicité (MFP), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Epidémiologie des Maladies Emergentes, Pasteur-Cnam risques infectieux et émergents (PACRI), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Equipe avenir Microorganismes et Barrières de l'Hôte, CHU Necker - Enfants Malades [AP-HP], ANR-10-LABX-62-IBEID,IBEID,Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'(2010), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional de La Réunion ( CHR Réunion ), Biologie des Infections, Institut Pasteur [Paris]-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Conservatoire National des Arts et Métiers [CNAM] ( CNAM ) -Institut Pasteur [Paris]-Pasteur-Cnam risques infectieux et émergents ( PACRI ), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] ( CNAM ), BIOlogie GEstion des Risques en agriculture - Champignons Pathogènes des Plantes ( BIOGER-CPP ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, CNRS-UMR 5234, Microbiologie fondamentale et Pathogénicité, University of Bordeaux 2, Bordeaux, France, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Universitaire de La Réunion ( CHU La Réunion ), and ANR-10-LABX-62-IBEID,IBEID,Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases' ( 2010 )
Background Arthritogenic alphaviruses, including Chikungunya virus (CHIKV), are responsible for acute fever and arthralgia, but can also lead to chronic symptoms. In 2006, a Chikungunya outbreak occurred in La Réunion Island, during which we constituted a prospective cohort of viremic patients (n = 180) and defined the clinical and biological features of acute infection. Individuals were followed as part of a longitudinal study to investigate in details the long-term outcome of Chikungunya. Methodology/Principal Findings Patients were submitted to clinical investigations 4, 6, 14 and 36 months after presentation with acute CHIKV infection. At 36 months, 22 patients with arthralgia and 20 patients without arthralgia were randomly selected from the cohort and consented for blood sampling. During the 3 years following acute infection, 60% of patients had experienced symptoms of arthralgia, with most reporting episodic relapse and recovery periods. Long-term arthralgias were typically polyarthralgia (70%), that were usually symmetrical (90%) and highly incapacitating (77%). They were often associated with local swelling (63%), asthenia (77%) or depression (56%). The age over 35 years and the presence of arthralgia 4 months after the disease onset are risk factors of long-term arthralgia. Patients with long-term arthralgia did not display biological markers typically found in autoimmune or rheumatoid diseases. These data helped define the features of CHIKV-associated chronic arthralgia and permitted an estimation of the economic burden associated with arthralgia. Conclusions/Significance This study demonstrates that chronic arthralgia is a frequent complication of acute Chikungunya disease and suggests that it results from a local rather than systemic inflammation., Author Summary Chikungunya virus (CHIKV) is transmitted to human by mosquitoes. It is a re-emerging virus that has a risk to spread globally, given the expanding dissemination of its mosquito vectors. Chikungunya disease is characterized by acute transient febrile arthralgic illness, but can also lead to chronic incapacitating arthralgia. We have conducted a prospective longitudinal study to investigate in details long-term outcome of CHIKV infection. We found that 60% of patients experienced arthralgia 36 months after the onset of acute disease. Arthralgia affected most often multiple sites and were usually incapacitating. In addition to arthralgia, many patients suffered from myalgia and cutaneous lesions and several cognitive dysfunctions. We also showed that age over 35 years and the presence of arthralgia 4 months after the onset of disease are risk factors for long-term arthralgia. Patients with long-term arthralgia did not display biological markers typically found in autoimmune or rheumatoid diseases. This study demonstrates that chronic arthralgia is a frequent complication of acute Chikungunya disease and suggests that it results from a local rather than systemic inflammation.