International audienceAlphaviruses, including Chikungunya virus (CHIKV), produce a transient illness in humans, but severe forms leading to chronic incapacitating arthralgia/arthritis have been reported by mechanisms largely ill-characterized. The pathogenesis of CHIKV was addressed in a prospective cohort study of 49 hospitalized patients from Reunion Island subsequently categorized into two distinct groups at 12 mo postinfection. Comprehensive analyses of the clinical and immunological parameters throughout the disease course were analyzed in either the “recovered” or the “chronic” groups to identify prognostic markers of arthritis-like pathology after CHIKV disease. We found that the chronic group consisted mainly of more elderly patients (\textgreater60 y) and with much higher viral loads (up to 1010 viruses per milliliter of blood) during the acute phase. Remarkably, a rapid innate immune antiviral response was demonstrated by robust dendritic/NK/CD4/CD8 cell activation and accompanied by a rather weak Th1/Th2 cytokine response in both groups. Interestingly, the antiviral immune response witnessed by high levels of IFN-α mRNA in PBMCs and circulating IL-12 persisted for months only in the chronic group. CHIKV (RNA and proteins) was found in perivascular synovial macrophages in one chronic patient 18 mo postinfection surrounded by infiltrating NK and T cells (CD4++ but rare cytotoxic CD8). Fibroblast hyperplasia, strong angiogenesis, tissue lesions given the high levels of matrix metalloproteinase 2, and acute cell death [high cleaved poly(ADP-ribose) polymerase staining] were observed in the injured synovial tissue. These observed cellular and molecular events may contribute to chronic arthralgia/arthritis targeted by methotrexate used empirically for effective treatment but with immunosuppressive function in a context of viral persistence
BackgroundWith more than 300 million infections estimated annually worldwide, dengue is the most prevalent arboviral infection. On Reunion Island, after a large outbreak in 1977–78, only limited episodes of viral circulation or sporadic cases were reported till 2015.AimOur objective was to document and report on the circulation of dengue virus after the occurrence of a small outbreak during austral summer 2015/16 and until the large outbreak of 2018.MethodsBeside the mandatory notification of biologically confirmed dengue cases, additional systems of surveillance were set up: estimation of dengue-like syndrome in people seeking care by their family doctor, surveillance of emergency department visits related to dengue, surveillance of hospitalised dengue patients and deaths classifications.ResultsAfter a moderate outbreak during summer 2015/16 with 231 cases, 2017 was characterised by limited viral circulation (97 cases) which, however, persisted during the austral winter. By February 2018, the number of cases had increased and led to a peak at the beginning of May 2018. More than 6,000 cases were reported this year (dengue virus type 2 only). In addition, six deaths of dengue patients were notified.ConclusionIn 2017, the persistence of transmission during winter created favourable conditions for the emergence of an epidemic during summer 2018. After this moderate epidemic wave, the viral circulation persisted during winter 2018 for the second year, opening the door for the second wave in 2019 and for potential endemisation of the disease on Reunion Island in the near future.
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