A226V Strains of Chikungunya Virus, Réunion Island, 2010

International audienceChikungunya virus (CHIKV) first emerged in Indian Ocean islands off the eastern coast of Africa in 2005 and was responsible for large-scale epidemics on the islands of Réunion, Comoros, Mayotte, Mauritius, Madagascar, and Seychelles (1–4). On Réunion Island, a French overseas territory of 810,000 inhabitants, herd immunity reached 38% in October 2006 (5). Molecular epidemiology of the strain responsible for these outbreaks indicated that it had originated in Kenya (6). The epidemic on Réunion Island was associated with a mutation in the envelope protein gene (E1-A226V) that improves replication and transmission efficiency in Aedes albopictus mosquitoes (7)

Human leptospirosis on Reunion Island, Indian Ocean: are rodents the (only) ones to blame?

Background: Although leptospirosis is a zoonosis of major concern on tropical islands, the molecular epidemiology of the disease aiming at linking human cases to specific animal reservoirs has been rarely explored within these peculiar ecosystems. Methodology/Principal Findings: Five species of wild small mammals (n = 995) as well as domestic animals (n = 101) were screened for Leptospira infection on Reunion Island; positive samples were subsequently genotyped and compared to Leptospira from clinical cases diagnosed in 2012–2013 (n = 66), using MLST analysis. We identified two pathogenic species in human cases, namely Leptospira interrogans and Leptospira borgpetersenii. Leptospira interrogans was by far dominant both in clinical samples (96.6%) and in infected animal samples (95.8%), with Rattus spp and dogs being its exclusive carriers. The genetic diversity within L. interrogans was apparently limited to two sequence types (STs): ST02, identified among most clinical samples and in all rats with complete MLST, and ST34, identified in six humans, but not in rats. Noteworthy, L. interrogans detected in two stray dogs partially matched with ST02 and ST34. Leptospira borgpetersenii was identified in two clinical samples only (3.4%), as well as in cows and mice; four haplotypes were identified, of which two seemingly identical in clinical and animal samples. Leptospira borgpetersenii haplotypes detected in human cases were clearly distinct from the lineage detected so far in the endemic bat species Mormopterus francoismoutoui, thus excluding a role for this volant mammal in the local human epidemiology of the disease. Conclusions/Significance: Our data confirm rats as a major reservoir of Leptospira on Reunion Island, but also pinpoint a possible role of dogs, cows and mice in the local epidemiology of human leptospirosis. This study shows that a comprehensive molecular characterization of pathogenic Leptospira in both clinical and animal samples helps to gaining insight into leptospirosis epidemiology within a specific environmental setting

Intensive Care Unit Admission for Pandemic (H1N1) 2009, Reunion Island, 2009

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Chikungunya Virus Infection during Pregnancy, Réunion, France, 2006

Except for prenatal hospital admissions for those infected, this virus had no effect on outcomes

Low Clinical Burden of 2009 Pandemic Influenza A (H1N1) Infection during Pregnancy on the Island of La Réunion

BACKGROUND: Pregnant women have been identified as a group at risk, both for respiratory complications than for the admissions to the Intensive Care Unit (ICU) during the 2009 H1N1 influenza pandemic (pdm). The purpose of this prospective register-based cohort-study was to characterize the clinical virulence of the pdm (H1N1/09)v during pregnancy in La Réunion. METHODS/PRINCIPAL FINDINGS: Over a twelve-week pdm wave (13 July to 3 October 2009), 294 pregnant women presented with an influenza-like illness (ILI) to one of the three maternity departments of the South Reunion area, Indian Ocean. Out of these, 278 were checked by RT-PCR for influenza viruses (157 positive and 121 negative, of whom, 141 with pdm flu and 132 with ILIs of non pdm origin, 5 untyped). The median body temperature was higher in women experiencing pdm flu than in those with non pdm ILI (38.9 degrees C versus 38.3 degrees C, P<0.0001), without evidence linked to circulating viremia. Oseltamivir was given for 86% of pdm flu cases in a median time inferior than 48 hrs (range 0-7 days). The hospitalization rate for pdm flu was of 60% and not associated with underlying conditions. Six viral pneumonia and fourteen asthma attacks were observed among 84 hospitalized pdm flu cases, of whom, only one led to the ICU for an acute lung injury. No maternal death occurred during the pdm wave. None adverse pregnancy outcome was associated with pdm flu. No congenital birth defect, nor early-onset neonatal influenza infection was attributable to pdm flu exposure. CONCLUSIONS/SIGNIFICANCE: This report mitigates substantially the presumed severity of pandemic H1N1/09 influenza infection during pregnancy. The reasons for which the clinical burden of H1N1/09 influenza virus may differ worldwide raise questions about a differential local viral-strain effect and public health preparedness, notably in timely access to special care and antiviral treatments

Physiopathology of chikungunya in acute and chronic stages of the disease in human

Chikungunya est un alphavirus transmis par les moustiques (Aedes) et qui provoque de la fièvre, des éruptions cutanées, des myalgies et des arthralgies. La maladie (CHIKVD) est transitoire, mais des formes sévères menant à des arthrites chroniques incapacitantes ont été signalées. Nous avons dans un premier temps étudié prospectivement les paramètres cliniques et immunologiques associés à la maladie chez des patients hospitalisés et identifiés comme étant ‘guéris’ ou 'chronique' à M12 après l'infection. Dans la deuxième partie, nous avons observé in vitro les mécanismes et le rôle de l'apoptose dans le processus infectieux permettant au virus de persister dans les sanctuaires tissulaires. En phase aiguë, une forte réponse immune dominée par une activation des cellules NK/dendritique/cellules T, la production d’anticorps spécifiques et une faible production de cytokines Th1 > Th2 a été observée mais sans aucune différence significative entre les deux groupes. Cependant, la virémie initiale s'est révélée beaucoup plus élevée dans le groupe chronique est nous avons pu identifier du matériel viral dans les macrophages du tissu synovial d'un patient chronique post-CHIKVD (M18). Dans la deuxième partie de l'étude, nous avons constaté que CHIKV est capable d'induire l'apoptose par la voie intrinsèque et extrinsèque et également par un mécanisme ‘bystander’. De plus, nous avons observé que le CHIKV présent dans des corps (blebs) apoptotiques était capable d'infecter les cellules voisines (Hela et macrophage MM6). Notre étude a permis de mettre en évidence pour la première fois que CHIKV contrôle et détourne à son profit les mécanismes de défense anti-infectieux.Chikungunya is an Alphavirus transmitted by mosquitoes (Aedes) and which causes fever, rash, myalgia and arthralgia. The disease (CHIKVD) is transient but severe forms leading to chronic incapacitating arthritis have been reported. The study involved first a prospective cohort study of hospitalized patients from Reunion Island subsequently categorized into ‘recovered’ or ‘chronic arthralgia’ groups at M12 post infection. Clinical and immunological parameters were measured throughout the disease course. In part two, we addressed in vitro the role of apoptosis in the infection process and particularly to ascertain the mechanisms allowing the virus to persist in tissue sanctuaries. We observed that a rapid immune antiviral response was evidenced by the robust dendritic/NK//T cell activation and accompanied by a specific IgM/IgG response and a rather weak Th1/Th2 cytokine response in both groups. The viremia was much more pronounced in the chronic group and, critically, we found that CHIKV was persisting (M18) in perivascular synovial macrophages. Fibroblast hyperplasia, strong angiogenesis and acute cell deaths were observed in the injured synovial tissue. In the second part of the study, we found that CHIKV was able to trigger apoptosis through intrinsic and extrinsic pathways. Bystander apoptosis was also evidenced in neighboring cells in a caspase 8-dependent manner. Remarkably, CHIKV hiding into apoptotic blebs was able to infect neighboring cells and these events were inhibited specifically by inhibitors of caspases, blebbing and engulfment. We herein describe a novel mechanism by which CHIKV invades and escapes the host immune response and contribute to chronic arthralgia/arthritis

Étude de la physiopathologie de l'infection Chikungunya en phase aiguë et chronique chez l'homme

Chikungunya is an Alphavirus transmitted by mosquitoes (Aedes) and which causes fever, rash, myalgia and arthralgia. The disease (CHIKVD) is transient but severe forms leading to chronic incapacitating arthritis have been reported. The study involved first a prospective cohort study of hospitalized patients from Reunion Island subsequently categorized into ‘recovered’ or ‘chronic arthralgia’ groups at M12 post infection. Clinical and immunological parameters were measured throughout the disease course. In part two, we addressed in vitro the role of apoptosis in the infection process and particularly to ascertain the mechanisms allowing the virus to persist in tissue sanctuaries. We observed that a rapid immune antiviral response was evidenced by the robust dendritic/NK//T cell activation and accompanied by a specific IgM/IgG response and a rather weak Th1/Th2 cytokine response in both groups. The viremia was much more pronounced in the chronic group and, critically, we found that CHIKV was persisting (M18) in perivascular synovial macrophages. Fibroblast hyperplasia, strong angiogenesis and acute cell deaths were observed in the injured synovial tissue. In the second part of the study, we found that CHIKV was able to trigger apoptosis through intrinsic and extrinsic pathways. Bystander apoptosis was also evidenced in neighboring cells in a caspase 8-dependent manner. Remarkably, CHIKV hiding into apoptotic blebs was able to infect neighboring cells and these events were inhibited specifically by inhibitors of caspases, blebbing and engulfment. We herein describe a novel mechanism by which CHIKV invades and escapes the host immune response and contribute to chronic arthralgia/arthritis.Chikungunya est un alphavirus transmis par les moustiques (Aedes) et qui provoque de la fièvre, des éruptions cutanées, des myalgies et des arthralgies. La maladie (CHIKVD) est transitoire, mais des formes sévères menant à des arthrites chroniques incapacitantes ont été signalées. Nous avons dans un premier temps étudié prospectivement les paramètres cliniques et immunologiques associés à la maladie chez des patients hospitalisés et identifiés comme étant ‘guéris’ ou 'chronique' à M12 après l'infection. Dans la deuxième partie, nous avons observé in vitro les mécanismes et le rôle de l'apoptose dans le processus infectieux permettant au virus de persister dans les sanctuaires tissulaires. En phase aiguë, une forte réponse immune dominée par une activation des cellules NK/dendritique/cellules T, la production d’anticorps spécifiques et une faible production de cytokines Th1 > Th2 a été observée mais sans aucune différence significative entre les deux groupes. Cependant, la virémie initiale s'est révélée beaucoup plus élevée dans le groupe chronique est nous avons pu identifier du matériel viral dans les macrophages du tissu synovial d'un patient chronique post-CHIKVD (M18). Dans la deuxième partie de l'étude, nous avons constaté que CHIKV est capable d'induire l'apoptose par la voie intrinsèque et extrinsèque et également par un mécanisme ‘bystander’. De plus, nous avons observé que le CHIKV présent dans des corps (blebs) apoptotiques était capable d'infecter les cellules voisines (Hela et macrophage MM6). Notre étude a permis de mettre en évidence pour la première fois que CHIKV contrôle et détourne à son profit les mécanismes de défense anti-infectieux

The immunology and inflammatory responses of human melanocytes in infectious diseases

International audienceMelanin is a canonical and major defense molecule in invertebrates but its role in mammalian immunity remains unexplored. In contrast, several recent studies have highlighted the emerging innate immune activities of human melanin-producing cells which can sense and respond to bacterial and viral infections. Indeed, the skin is a major portal of entry for pathogens such as arboviruses (Chikungunya, Dengue) and bacteria (mycobacterium leprae, Leptospira spirochetes). Melanocytes of the epidermis could contribute to the phagocytosis of these invading pathogens and to present antigens to competent immune cells. Melanocytes are known to produce key cytokines such as IL-1β, IL6 and TNF-α as well as chemokines. These molecules will subsequently alert macrophages, neutrophils, fibroblasts and keratinocytes through unique crosstalk mechanisms. The infection and the inflammatory responses will control melanocyte's immune and metabolic functions and could contribute to skin manifestations (rash, hyper or de-pigmentation, epidermolysis and psoriasis-like lesions). This review will address the potential role of melanocytes in immunity, inflammation and infection of the skin in health and diseases