Institute Pasteur Of Nouvelle Caledonie

Nouméa, New Caledonia

Institute Pasteur Of Nouvelle Caledonie

Nouméa, New Caledonia
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Matsui M.,Institute Pasteur Of Nouvelle Caledonie | Bruyere-Ostells L.,Institute Pasteur Of Nouvelle Caledonie | Goarant C.,Institute Pasteur Of Nouvelle Caledonie
Infection and Immunity | Year: 2011

Leptospirosis is a widespread zoonosis characterized by multiple organ failure and variable host susceptibility toward pathogenic Leptospira strains. In this study, we put the role of inflammatory mediators in parallel with bacterial burdens and organ lesions by comparing a susceptible animal model, the hamster, and a resistant one, the Oncins France 1 (OF1) mouse, both infected with virulent Leptospira interrogans serovar Icterohaemorrhagiae strain Verdun. Histological observations evidenced edema, congestion, hemorrhage, and inflammatory infiltration in the organs of hamsters, in contrast to limited changes in mice. Using reverse transcription-quantitative PCR techniques, we showed that the relative Leptospira burden progressively increased in hamster tissues, while a rapid clearance was observed in mouse tissues. The early regulation of the proinflammatory mediators interleukin-1β (IL-1β), IL-6, tumor necrosis factor alpha, and cyclo-oxygenase-2 and the chemokines gamma interferon-inducible protein 10 kDa/CXCL10 and macrophage inflammatory protein-1α/CCL3 in mouse tissues contrasted with their delayed and massive overexpression in hamster tissues. Conversely, the induction of the anti-inflammatory cytokine IL-10 was faster in the resistant than in the susceptible animal model. The role of these cytokines in the pathophysiology of leptospirosis and the implications of their differential regulation in the development of this disease are discussed. © 2011, American Society for Microbiology.


Roth A.,Secretariat of the Pacific Community | Mercier A.,Secretariat of the Pacific Community | Lepers C.,Secretariat of the Pacific Community | Hoy D.,Secretariat of the Pacific Community | And 4 more authors.
Eurosurveillance | Year: 2014

Since January 2012, the Pacific Region has experienced 28 new documented outbreaks and circulation of dengue, chikungunya and Zika virus. These mosquito- borne disease epidemics seem to become more frequent and diverse, and it is likely that this is only the early stages of a wave that will continue for several years. Improved surveillance and response measures are needed to mitigate the already heavy burden on island health systems and limit further spread to other parts of the world. © 2014, European Centre for Disease Prevention and Control (ECDC). All rights reserved.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC1-PM-22-2016 | Award Amount: 15.59M | Year: 2016

ZIKAlliance is a multidisciplinary project with a global One Health approach, built: on a multi-centric network of clinical cohorts in the Caribbean, Central & South America; research sites in countries where the virus has been or is currently circulating (Africa, Asia, Polynesia) or at risk for emergence (Reunion Island); a strong network of European and Brazilian clinical & basic research institutions; and multiple interfaces with other scientific and public health programmes. ZIKAlliance will addrees three key objectives relating to (i) impact of Zika virus (ZIKV) infection during pregnancy and short & medium term effects on newborns, (ii) associated natural history of ZIKV infection in humans and their environment in the context of other circulating arboviruses and (iii) building the overall capacity for preparedness research for future epidemic threats in Latin America & the Caribbean. The project will take advantage of large standardised clinical cohorts of pregnant women and febrile patients in regions of Latin America and the Caribbean were the virus is circulating, expanding a preexisting network established by the IDAMS EU project. I will also benefit of a very strong expertise in basic and environmental sciences, with access to both field work and sophisticated technological infrastructures to characterise virus replication and physiopathology mechanisms. To meet its 3 key objectives, the scientific project has been organised in 9 work packages, with WP2/3 dedicated to clinical research (cohorts, clinical biology, epidemiology & modeling), WP3/4 to basic research (virology & antivirals, pathophysiology & animal models), WP5/6 to environmental research (animal reservoirs, vectors & vector control) , WP7/8 to social sciences & communication, and WP9 to management. The broad consortium set-up allow gathering the necessary expertise for an actual interdisciplinary approach, and operating in a range of countries with contrasting ZIKV epidemiological status.


Baumann F.,Institute Pasteur Of Nouvelle Caledonie | Bourrat M.-B.,Nurse clinic Entraide sante | Pauillac S.,Institute Pasteur Of Nouvelle Caledonie
Toxicon | Year: 2010

Ciguatera is a widespread ichthyosarcotoxism which causes gastrointestinal, neurological and cardiovascular disturbances. Investigations conducted by ORSTOM in 1992 highlighted a prevalence of 25% in the adult population of Noumea, New Caledonia. The main objective of our study was to estimate the prevalence of ciguatera and the persistence of symptoms by sex and by ethnicity among adult patients of a nurse clinic in Noumea in 2005.Investigations were conducted from 1st January to 15th June 2005. During this period, 559 patients were included: 165 males and 394 females. Among them, 37.8% were poisoned at least once in their life. This rate was independent of gender and ethnicity, but was significantly higher in age groups above 40 years. Neurological signs were more frequent (>80%) than gastrointestinal (<50%) and cardiac signs (<15%). Symptoms presented no difference between ethnic or gender groups, even for subjective signs. Most of poisonings were due to carnivorous fishes, but quite all species living in the lagoon were quoted. Symptoms persisted more than one year for 34% of the population, in both Melanesians and Caucasians.This study shows a significant increase of ciguatera prevalence, and its chronicity for 1/5 of European cases. © 2009 Elsevier Ltd.


Tubiana S.,Institute Pasteur Of Nouvelle Caledonie | Mikulski M.,Center Hospitalier Territorial Of Noumea | Becam J.,Institute Pasteur Of Nouvelle Caledonie | Lacassin F.,Center Hospitalier Territorial Of Noumea | And 4 more authors.
PLoS Neglected Tropical Diseases | Year: 2013

Background: Leptospirosis is a major public health concern in New Caledonia (NC) and in other tropical countries. Severe manifestations of the disease are estimated to occur in 5-15% of all human infections worldwide and factors associated with these forms are poorly understood. Our objectives were to identify risk factors and predictors of severe forms of leptospirosis in adults. Methods and Findings: We conducted a retrospective case-control study of inpatients with laboratory-confirmed leptospirosis who were admitted to two public hospitals in NC in 2008-2011. Cases were patients with fatal or severe leptospirosis, as determined by clinical criteria. This approach was meant to be pragmatic and to reflect the routine medical management of patients. Controls were defined as patients hospitalized for milder leptospirosis. Risk and prognostic factors were identified by multivariate logistic regression. Among the 176 patients enrolled in the study, 71 had criteria of severity including 10 deaths (Case Fatality Rate = 14.1%). Three risk factors were independently associated with severe leptospirosis: current cigarette smoking (OR = 2.94 [CI 1.45-5.96]); delays >2 days between the onset of symptoms and the initiation of antibiotherapy (OR = 2.78 [CI 1.31-5.91]); and Leptospira interrogans serogroup Icterohaemorrhagiae as the infecting strain (OR = 2.79 [CI 1.26-6.18]). The following post-admission laboratory results correlated with poor prognoses: platelet count ≤50,000/μL (OR = 6.36 [CI 1.79-22.62]), serum creatinine >200 mM (OR = 5.86 [CI 1.61-21.27]), serum lactate >2.5 mM (OR = 5.14 [CI 1.57-16.87]), serum amylase >250 UI/L (OR = 4.66 [CI 1.39-15.69]) and leptospiremia >1000 leptospires/mL (OR = 4.31 [CI 1.17-15.92]). Conclusions: To assess the risk of developing severe leptospirosis, our study illustrates the benefit for clinicians to have: i) the identification of the infective strain, ii) a critical threshold of qPCR-determined leptospiremia and iii) early laboratory results. In New Caledonia, preventative measures should focus on early presumptive antibacterial therapy and on rodent (reservoir of Icterohaemorrhagiae serogroup) control. © 2013 Tubiana et al.


Perez J.,Institute Pasteur Of Nouvelle Caledonie
BMC microbiology | Year: 2010

Most of the current knowledge of leptospirosis epidemiology originates from serological results obtained with the reference Microscopic Agglutination Test (MAT). However, inconsistencies and weaknesses of this diagnostic technique are evident. A growing use of PCR has improved the early diagnosis of leptospirosis but a drawback is that it cannot provide information on the infecting Leptospira strain which provides important epidemiologic data. Our work is aimed at evaluating if the sequence polymorphism of diagnostic PCR products could be used to identify the infecting Leptospira strains in the New Caledonian environment. Both the lfb1 and secY diagnostic PCR products displayed a sequence polymorphism that could prove useful in presumptively identifying the infecting leptospire. Using both this polymorphism and MLST results with New Caledonian isolates and clinical samples, we confirmed the epidemiological relevance of the sequence-based identification of Leptospira strains. Additionally, we identified one cluster of L. interrogans that contained no reference strain and one cluster of L. borgpetersenii found only in the introduced Rusa deer Cervus timorensis russa that is its probable reservoir. The sequence polymorphism of diagnostic PCR products proved useful in presumptively identifying the infecting Leptospira strains. This could contribute to a better understanding of leptospirosis epidemiology by providing epidemiological information that cannot be directly attained from the use of PCR as an early diagnostic test for leptospirosis.


Vernel-Pauillac F.R.,Institute Pasteur Of Nouvelle Caledonie | Goarant C.,Institute Pasteur Of Nouvelle Caledonie
PLoS Neglected Tropical Diseases | Year: 2010

Background: Parameters predicting the evolution of leptospirosis would be useful for clinicians, as well as to better understand severe leptospirosis, but are scarce and rarely validated. Because severe leptospirosis includes septic shock, similarities with predictors evidenced for sepsis and septic shock were studied in a hamster model. Methodology/Principal Findings: Using an LD50 model of leptospirosis in hamsters, we first determined that 3 days postinfection was a time-point that allowed studying the regulation of immune gene expression and represented the onset of the clinical signs of the disease. In the absence of tools to assess serum concentrations of immune effectors in hamsters, we determined mRNA levels of various immune genes, especially cytokines, together with leptospiraemia at this particular time-point. We found differential expression of both pro- and anti-inflammatory mediators, with significantly higher expression levels of tumor necrosis factor α, interleukin 1α, cyclo-oxygenase 2 and interleukin 10 genes in nonsurvivors compared to survivors. Higher leptospiraemia was also observed in nonsurvivors. Lastly, we demonstrated the relevance of these results by comparing their respective expression levels using a LD100 model or an isogenic high-passage nonvirulent variant. Conclusions/Significance: Up-regulated gene expression of both pro- and anti-inflammatory immune effectors in hamsters with fatal outcome in an LD50 model of leptospirosis, together with a higher Leptospira burden, suggest that these gene expression levels could be predictors of adverse outcome in leptospirosis. © 2010 Vernel-Pauillac, Goarant.


Guerrier G.,Center Hospitalier Territorial | D'Ortenzio E.,Institute Pasteur Of Nouvelle Caledonie
PLoS ONE | Year: 2013

Background: Leptospirosis is an endemo-epidemic zoonotic disease associated with potentially fatal renal, cardiovascular or pulmonary failure. Recommended treatment includes antibiotics, which may induce a Jarisch-Herxheimer reaction (JHR). Since little information on the importance of this adverse event is available, we performed this review to quantify frequency and impact of JHR in leptospirosis management. Methodology/Principal Findings: This review systematically summarizes the literature on the JHR in leptospirosis. To approach the broader aspects of the subject, articles considering the treatment of leptospirosis, national leptospirosis guidelines and textbook and technical reports of the World Health Organisation were reviewed. Publications describing JHR in leptospirosis are very limited and consist mainly of single case reports and small case series. A single randomized control trial specifically assessed the JHR occurrence, but it has never been systematically investigated in large trials. Not all guidelines and not all literature on leptospirosis mention this reaction which can be fatal. Conclusions/Significance: Although generally assumed to be a rare event, the true prevalence of JHR in leptospirosis is unknown and the awareness of this event is insufficient. All leptospirosis guidelines and local leptospirosis protocols should stress on systematic monitoring for clinical status early after antibiotic administration. Large well designed studies are required to precise the incidence and the impact of JHR as well as the severity and rates between various antibiotics. © 2013 Guerrier, D'Ortenzio.


Matsui M.,Institute Pasteur Of Nouvelle Caledonie | Soupe M.E.,Institute Pasteur Of Nouvelle Caledonie | Becam J.,Institute Pasteur Of Nouvelle Caledonie | Goarant C.,Institute Pasteur Of Nouvelle Caledonie
Applied and Environmental Microbiology | Year: 2012

Transcripts of Leptospira 16S rRNA, FlaB, LigB, LipL21, LipL32, LipL36, LipL41, and OmpL37 were quantified in the blood of susceptible (hamsters) and resistant (mice) animal models of leptospirosis. We first validated adequate reference genes and then evaluated expression patterns in vivo compared to in vitro cultures. LipL32 expression was downregulated in vivo and differentially regulated in resistant and susceptible animals. FlaB expression was also repressed in mice but not in hamsters. In contrast, LigB and OmpL37 were upregulated in vivo. Thus, we demonstrated that a virulent strain of Leptospira differentially adapts its gene expression in the blood of infected animals. © 2012, American Society for Microbiology.


Perez J.,Institute Pasteur Of Nouvelle Caledonie | Brescia F.,Institute Agronomique neo Caledonien | Becam J.,Institute Pasteur Of Nouvelle Caledonie | Mauron C.,Institute Pasteur Of Nouvelle Caledonie | Goarant C.,Institute Pasteur Of Nouvelle Caledonie
PLoS Neglected Tropical Diseases | Year: 2011

Background: Widespread but particularly incident in the tropics, leptospirosis is transmitted to humans directly or indirectly by virtually any Mammal species. However, rodents are recognized as the most important reservoir. In endemic regions, seasonal outbreaks are observed during hot rainy periods. In such regions, hot spots can be evidenced, where leptospirosis is "hyper-endemic", its incidence reaching 500 annual cases per 100,000. A better knowledge of how rodent populations and their Leptospira prevalence respond to seasonal and meteorological fluctuations might help implement relevant control measures. Methodology/Principal Findings: In two tribes in New Caledonia with hyper-endemic leptospirosis, rodent abundance and Leptospira prevalence was studied twice a year, in hot and cool seasons for two consecutive years. Highly contrasted meteorological situations, particularly rainfall intensities, were noted between the two hot seasons studied. Our results show that during a hot and rainy period, both the rodent populations and their Leptospira carriage were higher. This pattern was more salient in commensal rodents than in the sylvatic rats. Conclusions/Significance: The dynamics of rodents and their Leptospira carriage changed during the survey, probably under the influence of meteorology. Rodents were both more numerous and more frequently carrying (therefore disseminating) leptospires during a hot rainy period, also corresponding to a flooding period with higher risks of human exposure to waters and watered soils. The outbreaks of leptospirosis in hyper-endemic areas could arise from meteorological conditions leading to both an increased risk of exposure of humans and an increased volume of the rodent reservoir. Rodent control measures would therefore be most effective during cool and dry seasons, when rodent populations and leptospirosis incidence are low. © 2011 Perez et al.

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