Alain Michault

Groupe Hospitalier Est Réunion (GHER), Réunion, Reunion

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Publications (110)278.69 Total impact

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    ABSTRACT: Chikungunya virus (CHIKV) is a re-emerging alphavirus that causes a debilitating arthritic disease, infects millions of people, and has no specific treatment. Like many alphaviruses, the structural targets on CHIKV that elicit a protective humoral immune response in humans are poorly defined. Here we used phage display against virus-like particles (VLPs) to isolate seven human monoclonal antibodies (MAbs) against the CHIKV envelope glycoproteins E2 and E1. One MAb, IM-CKV063, was highly neutralizing (IC50 7.4 ng/ml), demonstrated high-affinity binding (320 pM), and was capable of therapeutic and prophylactic protection in multiple animal models, up to 24 h post-exposure. Epitope mapping using a comprehensive shotgun mutagenesis library of 910 E2/E1 alanine mutations demonstrated that IM-CKV063 binds to an inter-subunit conformational epitope on domain A, a functionally important region of E2. MAbs against the highly conserved fusion loop have not previously been reported, but were also isolated in our studies. Fusion loop MAbs were broadly cross-reactive against diverse alphaviruses, but were non-neutralizing. Fusion loop MAb reactivity was affected by temperature and reactivity conditions, suggesting that the fusion loop is hidden in infectious virions. Visualizing the binding sites of 15 different MAbs on the structure of E2/E1 reveals that all epitopes are located at the membrane distal region of the E2/E1 spike. Interestingly, epitopes on the exposed top-most and outer surfaces of the E2/E1 trimer structure are neutralizing whereas epitopes facing the interior of the trimer are not, providing a rationale for vaccine design and therapeutic MAb development using the intact CHIKV E2/E1 trimer.
    Journal of Virology 10/2014; · 5.08 Impact Factor
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    ABSTRACT: Q fever is a widespread zoonosis that is caused by Coxiella burnetii (C. burnetii), and ruminants are identified as the main sources of human infections. Some human cases have been described, but very limited information was available about Q fever in ruminants on Reunion Island, a tropical island in the Indian Ocean. A cross-sectional study was undertaken from March 2011 to August 2012 to assess the Q fever prevalence and to identify the major risk factors of C. burnetii infection in ruminants. A total of 516 ruminants (245 cattle, 137 sheep and 134 goats) belonging to 71 farms and localized in different ecosystems of the island were randomly selected. Samples of blood, vaginal mucus and milk were concomitantly collected from females, and a questionnaire was submitted to the farmers. Ticks from positively detected farms were also collected. The overall seropositivity was 11.8% in cattle, 1.4% in sheep and 13.4% in goats. C. burnetii DNA was detected by PCR in 0.81%, 4.4% and 20.1% in cow, sheep and goat vaginal swabs, respectively. C. burnetii shedding in milk was observed in 1% of cows, 0% in sheep and 4.7% in goats. None of the ticks were detected to be positive for C. burnetii. C. burnetii infection increased when the farm was exposed to prevailing winds and when there were no specific precautions for a visitor before entering the farm, and they decreased when a proper quarantine was set up for any introduction of a new ruminant and when the animals returned to the farm at night. MLVA genotyping confirmed the role of these risk factors in infection.
    PLoS neglected tropical diseases. 08/2014; 8(8):e3055.
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    ABSTRACT: Little is known about the neurocognitive outcome in children exposed to perinatal mother-to-child Chikungunya virus (p-CHIKV) infection.
    PLoS neglected tropical diseases. 07/2014; 8(7):e2996.
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    Emerging Infectious Diseases 04/2014; 20(4):720-2. · 6.79 Impact Factor
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    ABSTRACT: Since 1953, leptospirosis has been recognized as a public health problem on Reunion Island. In 2004, was implemented a specific surveillance system that included systematic reporting and the realization of environmental investigations around hospitalized cases. Here, we present the synthesis of historical data and the assessment of 9 years of leptospirosis surveillance. From 2004 to 2012, 414 hospitalized cases were reported. Cases of leptospirosis occurred mostly during the rainy season from December to May. Approximately 41% of infections occurred at home, 12% of infections occurred during aquatic leisure and 5% of cases were linked to professional activities. Furthermore, for 41% of cases, the place of infection could not be determined due to the accumulation of residential and non-residential exposure. Most of the cases of leptospirosis were linked to rural areas or traditional, rural occupations. We did not observe a shift to recreational leptospirosis as described in some developed countries. According to the new surveillance system, the number of reported cases has regularly increased since 2004. This situation is in part due to the improvement of the system in the first years but also to a real increase in the number of detected cases due to the introduction of molecular methods and to increased biological investigation into the Dengue-like syndrome by medical practitioners on the island since the Chikungunya crisis in 2006. This increase is probably due to surveillance and diagnosis biases but need to be carefully monitored. Nevertheless, the possibility of an outbreak is always present due to climatic events, such as after the "hyacinth" hurricane in 1980.
    International Journal of Environmental Research and Public Health 01/2014; 11(1):968-82. · 2.00 Impact Factor
  • 01/2014; 19(39).
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    ABSTRACT: Immunity against dengue virus (DENV) on Reunion Island could play an important role in the risk of dengue outbreaks but is rather unknown. A study was performed to estimate seroprevalence of antibodies against DENV among blood donors. An age- and sex-stratified sample of 1825 sera was randomly selected. Overall seroprevalence was 3.1% (95% CI: 2.2-3.9%); seroprevalence increased with age and was much higher in women than in men. The low level of herd immunity is consistent with the absence of an endemic circulation of DENV, and makes it probable that Reunion Island will face future outbreaks.
    Transactions of the Royal Society of Tropical Medicine and Hygiene 12/2013; · 1.82 Impact Factor
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    ABSTRACT: To search for serological evidence of congenital infection in apparently healthy neonates born to women infected with the Chikungunya virus (CHIKV) during pregnancy, monitoring for CHIKV-specific antibodies was performed within the CHIMERE cohort study (Reunion island, 2006-2008). CHIKV-specific antibody kinetics showed no evidence of asymptomatic congenital infection as neonates were tested negative for CHIKV-specific IgM antibodies at birth and 368 infants with CHIKV-specific IgG antibodies seroreversed completely (mean seroreversion time: 7.7 months). Seroreversion time of transplacental CHIKV IgG antibodies was inversely correlated with the stage of pregnancy at which exposure took place and end-term small for gestational infants seroreversed earlier.
    The Journal of Infectious Diseases 12/2013; · 5.85 Impact Factor
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    Amélie Desvars, Alain Michault, Pascale Bourhy
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    ABSTRACT: In the past decade, leptospirosis has emerged as a major zoonosis with a worldwide distribution. The disease is caused by bacteria of the genus Leptospira. The western Indian Ocean includes more than one hundred tropical or subequatorial islands where leptospirosis constitutes a major public health problem. The clinical signs of the human disease are generally similar to an influenza-like syndrome, but acute forms of the disease are reported and mortality remains significant in this region. In animals, clinical forms are mainly asymptomatic but leptospirosis reduces the fertility of livestock, resulting in economic losses. The data available about human and animal leptospirosis in the western Indian Ocean islands are diverse: human leptospirosis has been extensively studied in Reunion Island, Mayotte, and the Seychelles, whereas the human clinical disease has never been described in Madagascar, Comoros, Mauritius, or Rodrigues, mainly because of the deficiency in appropriate medical and diagnostic structures. The rat is recognized as the major reservoir host for the bacteria on all islands, but recent data from Reunion Island indicates that almost all mammals can be a source of contamination. The incidence of leptospirosis in humans is highly seasonal, and linked to the rainy season, which is favorable for the environmental maintenance and transmission of the bacteria. The epidemiology of leptospirosis is fully island-dependent, related to the number of mammalian species, the origins of the introduced mammalian species, the relationships between humans and fauna, and environmental as well as cultural and socio-economic factors.
    Veterinary Research 09/2013; 44(1):80. · 3.43 Impact Factor
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    ABSTRACT: Introduction Le réseau SEGA compte 5 laboratoires de biologie moléculaire, répartis entre Maurice, Madagascar, La Réunion et les Seychelles, capables de réaliser le diagnostic du chikungunya (CHIKV) et de la dengue (DENV) par rt-PCR. Parmi ceux-ci deux ont acquis cette compétence relativement récemment. Depuis avril 2011, le réseau SEGA travaille sur le renforcement de la surveillance biologique régionale des arboviroses articulée à la surveillance syndromique des fièvres. En janvier 2012, les responsables de laboratoire de l’océan Indien ont exprimé le besoin de la mise en place d’un programme de contrôle qualité externe. Les objectifs du programme sont : i) déterminer les niveaux de compétence de chaque laboratoire ; ii) guider les laboratoires dans la mise en oeuvre d’éventuelles mesures correctives ; iii) permettre un travail de formation continue par la mise en réseau des laboratoires. Méthodes Le programme est organisé et suivi par un expert externe au réseau. Le principe est de faire analyser, 2 fois par an, par chacun des laboratoires un set de 10 échantillons contenant ou ne contenant pas du virus DENV ou CHIKV, sans co-infection. La composition du set est définie par le consultant et l’Unité de Veille Sanitaire du réseau SEGA (UVS) et ne sera pas communiquée. Les échantillons sont préparés sur papier buvard (903 Protein Saver Card) par le laboratoire Candos (Maurice) et remis à l’UVS qui procède à l’anonymisation, la composition des sets et à l’envoi postal vers les laboratoires. Résultats Mis à part un laboratoire qui n’a pu diagnostiquer les cas de CHIKV, tous les autres ont présenté des résultats satisfaisants à ce premier test. Cette première étude a permis d’identifier quelques erreurs qui pourraient permettre d’améliorer les procédures dans certains laboratoires telles que un résultat positif pour les deux virus sur un même échantillon, une inversion d’échantillons ou encore une erreur de saisie des résultats avec même valeur CT pour deux échantillons consécutifs. Discussion - conclusion Des améliorations, en particulier au niveau de l’interface web, sont également prévues dans l’organisation de la prochaine évaluation. Un suivi est actuellement assuré auprès des laboratoires afin de proposer des mesures correctives et d’aider à développer ou améliorer les manuels de procédures standardisées. La deuxième évaluation est prévue pour fin juin 2013.
    orum International Veille Sanitaire et Réponse en Territoires Insulaires, Saint Denis, La Réunion; 06/2013
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    ABSTRACT: A 58-year-old woman living in Reunion Island and returning from Madagascar was hospitalized for neuroinvasive encephalitis and died 1 month later. West Nile virus (WNV) infection was biologically confirmed by detection of immunoglobulin M (IgM) reactive with WNV antigens in both cerebrospinal fluid and serum, and weak neutralizing activity was also detected. A veterinary survey performed in her traveling area showed a seroprevalence of WNV of 28.7% (95% confidence interval [CI] = 21.1-36.3) in adult poultry, confirming an active circulation of the virus. Development of a severe form could be related to a weak antibody response, because the patient presented low IgM and IgG titers. This case report underlines the constant risk of emergence of West Nile in Indian Ocean territories, including Reunion Island where competent vectors are widely present during the whole year.
    The American journal of tropical medicine and hygiene 06/2013; · 2.53 Impact Factor
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    ABSTRACT: Leptospirosis is the major infectious disease on Reunion Island but little is known about the animal reservoir. We conducted a wide-ranging survey that included samples from 574 animals belonging to 12 species. The seroprevalence and prevalence of renal carriage varied greatly depending on the species, with the highest seroprevalence (79·5%) found in Norway rats, and the lowest (13·2%) in tenrecs. The renal carriage rate ranged from 84·6% in mice to 0% in tenrecs. Our results suggest that rodents are the most important reservoirs of leptospirosis on Reunion Island. The epidemiological role that animals play in human infection is discussed. For the first time, we quantified the renal concentration of leptospires in ten naturally infected mammals. The history of Reunion Island colonization probably explains why the circulating Leptospira serogroups were similar to those found in Europe. Our study provides evidence that will help implement preventive measures against this zoonosis.
    Epidemiology and Infection 06/2013; 141(06). · 2.87 Impact Factor
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    ABSTRACT: 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. METHODOLOGYPRINCIPAL 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. CONCLUSIONSSIGNIFICANCE: 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.
    PLoS Neglected Tropical Diseases 03/2013; 7(3):e2137. · 4.57 Impact Factor
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    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 [greater than or equal to] 15 years) having declared RMSP at disease onset were extracted from the TELECHIK cohort study, Reunion island, and analysed 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 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.
    Arthritis research & therapy 01/2013; 15(1):R9. · 4.27 Impact Factor
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    ABSTRACT: The mosquito-borne alphavirus, chikungunya virus (CHIKV), has recently reemerged, producing the largest epidemic ever recorded for this virus, with up to 6.5 million cases of acute and chronic rheumatic disease. There are currently no licensed vaccines for CHIKV and current anti-inflammatory drug treatment is often inadequate. Here we describe the isolation and characterization of two human monoclonal antibodies, C9 and E8, from CHIKV infected and recovered individuals. C9 was determined to be a potent virus neutralizing antibody and a biosensor antibody binding study demonstrated it recognized residues on intact CHIKV VLPs. Shotgun mutagenesis alanine scanning of 98 percent of the residues in the E1 and E2 glycoproteins of CHIKV envelope showed that the epitope bound by C9 included amino-acid 162 in the acid-sensitive region (ASR) of the CHIKV E2 glycoprotein. The ASR is critical for the rearrangement of CHIKV E2 during fusion and viral entry into host cells, and we predict that C9 prevents these events from occurring. When used prophylactically in a CHIKV mouse model, C9 completely protected against CHIKV viremia and arthritis. We also observed that when administered therapeutically at 8 or 18 hours post-CHIKV challenge, C9 gave 100% protection in a pathogenic mouse model. Given that targeting this novel neutralizing epitope in E2 can potently protect both in vitro and in vivo, it is likely to be an important region both for future antibody and vaccine-based interventions against CHIKV.
    PLoS Neglected Tropical Diseases 01/2013; 7(9):e2423. · 4.57 Impact Factor
  • A Desvars, A Michault, F Chiroleu
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    ABSTRACT: In 2009, a survey was conducted in Reunion Island to determine the renal leptospiral load in black rats trapped in the field. The concentration of leptospires in kidney tissue was calculated using qPCR. Our results showed high inter-individual variations of renal bacterial load in naturally infected black rats (mean=8.27±4.72 log-genome copies per mg kidney tissue). The objective of this study was to model the renal leptospiral load in 50 naturally infected black rats as a function of sex, age, and weight. Statistical analysis by sex showed that, in naturally infected males, the renal leptospiral load was correlated with weight (p-value=0.032). Moreover, our model showed that weight and sex were significant explanatory variables for the renal leptospiral load in naturally infected young black rats (R(2)=0.953). Laboratory experimentation could not replicate naturally acquired infection, but field studies also present many limitations. Our study is the first attempt to explain individual variations in the renal leptospiral load in naturally infected reservoir animals but further research is needed.
    Acta tropica 12/2012; · 2.79 Impact Factor
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    ABSTRACT: On 16 November, 2011, a 59-year-old French man was admitted to a Mauritius hospital for a decompression sickness.…
    Journal of clinical microbiology 09/2012; 50(11):3812. · 4.16 Impact Factor
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    ABSTRACT: Our objective was to identify local animal reservoirs of leptospirosis to explain the unusual features of Leptospira strains recently described among patients on the island of Mayotte. By means of a microscopic agglutination test using local clinical isolates, we found that 11.2% of black rats were seropositive to Leptospira, whereas 10.2% of flying foxes, 2% of lemurs, 93.1% of domestic dogs, and 87.5% of stray dogs were seropositive. As observed in humans, Mini was the main serogroup circulating in animals, whereas serogroup Icterohaemorrhagiae was absent. Using quantitative polymerase chain reaction, we also showed that 29.8% of rats carried leptospires in their kidneys. The sequencing of 16S rRNA gene sequences of Leptospira found in black rat kidneys identified four genomospecies (Leptospira borgpetersenii, Leptospira interrogans, Leptospira kirschneri, and L. borgpetersenii group B), which established black rats as the major source of leptospirosis transmission to humans. The origins of such a genetic diversity in Leptospira strains are discussed.
    The American journal of tropical medicine and hygiene 07/2012; 87(1):134-40. · 2.53 Impact Factor
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    ABSTRACT: Persistence of clinical manifestations, especially polyarthralgia and fatigue, is a characteristic feature of chikungunya virus (CHIK-v) infection. The purpose of this study was to measure the impact of prolonged or late-onset manifestations of CHIK-v infection on the self-perceived health of people on Reunion Island. This retrospective cohort survey, dubbed TELECHIK survey, was conducted eighteen months after the end of the chikungunya outbreak on a representative random sample from the SEROCHIK population-based survey conducted on Reunion Island. A total of 1094 subjects whose CHIK-v specific IgG antibody status had been documented were interviewed about current symptoms. Analysis of data showed 45% of CHIK+ vs 14% of CHIK- subjects reporting musculoskeletal pain (P < 0.001), 56% vs. 44% reporting fatigue (P = 0.003), 77% vs. 53% reporting cerebral manifestations (P < 0.001), 51% vs. 34% reporting sensorineural impairments (P < 0.001), 18% vs. 13% reporting digestive complaints (P = 0.06), and 38% vs. 32% reporting skin involvement (P = 0.13). The mean delay between infection and interview was two years (range, 15-34 months). Analysis of data after correction for age, gender, body mass index and comorbidity indicated that rheumatic pain, fatigue, cerebral manifestations and sensorineural impairments were more likely in CHIK+ than CHIK- subjects but the likelihood of digestive and skin manifestations was the same. With a mean delay of two years after infection, 45% to 77% of CHIK+ subjects reported prolonged or late-onset symptoms attributable to CHIK-v. These results indicate that persistent manifestations of chikungunya infection have a heavy impact on rheumatologic, neurological and sensorineural health.
    Médecine tropicale: revue du Corps de santé colonial 03/2012; 72 Spec No:76-82.

Publication Stats

2k Citations
278.69 Total Impact Points

Institutions

  • 2007–2014
    • Groupe Hospitalier Est Réunion (GHER)
      Réunion, Reunion
  • 2013
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 2011–2013
    • Cirad - La recherche agronomique pour le développement
      • Centre de Coopération Internationale en Recherche Agronomique pour le Développement (CIRAD)
      Montpelhièr, Languedoc-Roussillon, France
    • Centre de Recherche et de Veille sur les Maladies Emergentes dans l’Océan Indien
      Saint-Denis, Réunion, Reunion
  • 2010–2012
    • Centre Hospitalier Universitaire de la Réunion
      Réunion, Reunion
    • University of La Réunion
      • Plant Communities and Biological Invaders in Tropical Environment (PVBMT)
      Saint-Denis, Réunion, Reunion
  • 2009–2012
    • Institut de veille sanitaire
      Charenton, Île-de-France, France
    • Office National de la Chasse et de la Faune Sauvage
      Lutetia Parisorum, Île-de-France, France