INTRODUCTION:No treatment hierarchy for external anogenital warts (AGW) is currently recommended, despite wide variations in the costs of available treatments. The aim of this study was to propose a treatment hierarchy based on a health economic analysis of local treatments for AGW from the perspective of the French health insurance system. METHODS:Thirteen treatments and 73 treatment sequences were evaluated for AGW clearance and absence of AGW recurrence at 3 months of follow-up. The cost per treatment included the cost of consultations, drugs, medical procedures, and dressings. The time horizon was one year. The least expensive treatment was used as the reference treatment in the calculation of incremental cost-effectiveness ratios (ICERs). A two-line decision tree for treatment was constructed. RESULTS:Podophyllotoxin 0.5% solution was the least expensive treatment. Compared to podophyllotoxin 0.5% solution, the most cost-effective treatment was surgical excision (ICER: €456.82) and the most cost-effective treatment sequence was podophyllotoxin 0.5% solution followed by 5-fluorouracil (5-FU) 5% cream. CONCLUSION:Considering the high risk of bias in the randomized controlled trials considered, the most cost-effective treatment sequence was podophyllotoxin 0.5% solution followed by 5-FU 5% cream.

BACKGROUND:In Reunion Island, dengue outbreaks have been occurring since 2018. The healthcare facilities are facing the problem of managing a massive influx of patients and a growing care burden. The aim of this study was to evaluate the performance of the SD Bioline Dengue Duo rapid diagnostic test in adults consulting at an emergency department during the 2019 epidemic.METHODOLOGY/PRINCIPAL FINDINGS:This retrospective study of diagnostic accuracy included patients over 18 years old, suspected of dengue, who were admitted to emergency units of the University Hospital of Reunion between the 1st of January and 30th of June, 2019, and were tested for dengue fever with the SD Bioline Dengue Duo rapid diagnostic test and reverse transcriptase polymerase chain reaction. Over the study period, 2099 patients were screened retrospectively. Of them, 671 patients matched the inclusion criteria. The overall rapid diagnostic test performance was 42% for sensitivity and 15% for specificity. The non-structural 1 antigen component had a good specificity of 82% but a low sensitivity of 12%. The immunoglobulin M component had a sensitivity of 28% and a specificity of 33%. Sensitivities were slightly improved beyond the 5th day of illness compared to the early stage for all components, but only the non-structural 1 antigen component had a better specificity of 91%. Furthermore, predictive values were low and post-test probabilities never improved pre-test probabilities in our setting.CONCLUSIONS/SIGNIFICANCE:These results suggest that the SD Bioline Dengue Duo RDT did not achieve sufficient performance levels to rule in, or discard, an early point of care dengue diagnosis in the emergency department during the 2019 epidemic in Reunion.

De nombreuses thérapeutiques sont disponibles pour le traitement des condylomes ano-génitaux externes (CAE), cependant aucune hiérarchie thérapeutique n'est clairement proposée à ce jour dans les dernières recommandations. L'objectif de ce travail était de réaliser une hiérarchisation des différentes thérapeutiques locales des CAE à travers une approche médicoéconomique selon la perspective de l'assurance maladie française. Les traitements évalués ont été identifiés à travers les dernières recommandations et revue systématique de la littérature. Ils ont été analysés en deux étapes, séparément puis par association de deux traitements différents. Le critère d'efficacité était la probabilité de succès thérapeutique qui combine la clairance des CAE à la fin du traitement et l'absence de récurrence des CAE jusqu'à la fin du suivi de 3 mois. La probabilité de succès d'un schéma thérapeutique était déterminée à l'aide des probabilités de clairance et de récurrence des deux traitements qui le composaient et suivant le modèle d'arbre de décision à deux lignes de traitement. Les coûts considérés par traitement comprenaient les coûts des consultations, des médicaments, des actes thérapeutiques et des pansements remboursés par l'assurance maladie française. L'horizon temporel était d'une année. Le traitement le moins coûteux était utilisé comme traitement de référence dans toutes les analyses. Le traitement le moins coûteux était la podophyllotoxine 0,5 % solution (11,1€) et a été considéré comme le traitement de référence dans nos analyses médico-économiques. Les analyses montraient que parmi les 13 traitements locaux évalués, l'exérèse chirurgicale était le traitement le plus efficient avec un ratio différentiel coût-résultat (RDCR) de 410,9€ par succès thérapeutique supplémentaire (STS). Parmi les 73 schémas thérapeutiques, le schéma thérapeutique le plus efficient était la podophyllotoxine 0,5 % solution suivie, en cas d'échec thérapeutique, du 5-fluorouracile 5 % crème avec un RDCR de 209,5€ par STS par rapport à la podophyllotoxine 0,5 % solution. Avec les réserves liées au haut risque de biais de la quasi-totalité des essais contrôlés inclus dans les revues systématiques prises en compte, cette évaluation médicoéconomique des traitements locaux des CAE semble montrer que par rapport à la podophyllotoxine 0,5 % solution, le traitement isolé le plus efficient serait l'exérèse chirurgicale. Le schéma thérapeutique le plus efficient serait la podophyllotoxine 0,5% solution suivie du 5-fluorouracile 5 % crème.

Aims LMNA-linked familial partial lipodystrophy type 2 (FPLD2) leads to insulin resistance-associated metabolic complications and cardiovascular diseases. We aimed to characterise the disease phenotype in a cohort of patients carrying an LMNA founder variant. Methods We collected clinical and biological data from patients carrying the monoallelic or biallelic LMNA p.(Thr655Asnfs*49) variant (n = 65 and 13, respectively) and 19 non-affected relative controls followed-up in Reunion Island Lipodystrophy Competence Centre, France. Results Two-thirds of patients with FPLD2 (n = 51) and one-third of controls (n = 6) displayed lipodystrophy and/or lean or android morphotype (P = 0.02). Although age and BMI were not statistically different between the two groups, the insulin resistance index (median HOMA-IR: 3.7 vs 1.5, P = 0.001), and the prevalence of diabetes, dyslipidaemia, and non-alcoholic fatty liver disease were much higher in patients with FPLD2 (51.3 vs 15.8%, 83.3 vs 42.1%, and 83.1 vs 33.3% (all P ≤ 0.01), respectively). Atherosclerosis tended to be more frequent in patients with FPLD2 (P = 0.07). Compared to heterozygous, homozygous patients displayed more severe lipoatrophy and metabolic alterations (lower BMI, fat mass, leptin and adiponectin, and higher triglycerides P ≤ 0.03) and tended to develop diabetes more frequently, and earlier (P = 0.09). Dilated cardiomyopathy and/or rhythm/conduction disturbances were the hallmark of the disease in homozygous patients, leading to death in four cases. Conclusions The level of expression of the LMNA ‘Reunionese’ variant determines the severity of both lipoatrophy and metabolic complications. It also modulates the cardiac phenotype, from atherosclerosis to severe cardiomyopathy, highlighting the need for careful cardiac follow-up in affected patients.

Epidemiological surveillance of Neisseria gonorrhoeae has become a major issue, due to the increasing number of cases and the emergence of multidrug-resistant clinical isolates.1 However, little is known about the epidemiology of N. gonorrhoeae in the Indian Ocean. We conducted a retrospective study between 20 October 2016 and 10 April 2017 to characterise the main circulating genotypes of N. gonorrhoeae and their resistance profiles on two islands in the Indian Ocean, Reunion and Mayotte. These islands are part of French overseas territories, and are populated by approximately 860 000 and 250 000 inhabitants, respectively. In total, 206 N. gonorrhoeae isolates were obtained within a network of 40 private and hospital laboratories, and 88 viable isolates (72 from Reunion and 16 from Mayotte) were selected at random for further microbiological and molecular investigations. Minimum inhibitory concentrations (MICs) were determined for six antibiotics using E-tests (Biomerieux, Marcy l’Etoile, France) and interpreted according to European Committee …

L'infection à virus Chikungunya (CHIKV) est une arbovirose dont les manifestations sont parfois prolongées et peuvent altérer durablement la qualité de vie en santé. La plupart des études de suivi des patients affectés par cette maladie reposent sur des cohortes hospitalières ou de sujets particuliers, sélectionnés par la gravité à l'inclusion. En 2015–2016, nous avons évalué la qualité de vie et les phénotypes douloureux en population générale sur un échantillon de sujets exposés au CHIKV lors d'une épidémie survenue en 2005–2006. À cette fin, une enquête téléphonique a été réalisée auprès d'un échantillon de 580 sujets issus d'une enquête de séroprevalence (2442 sujets à l'inclusion). Le critère d'évaluation principal était la composante physique du SF-36 (PCS). Les critères d'évaluation secondaire étaient la composante mentale (MCS) du SF-36, ainsi que les 8 dimensions de cette échelle de qualité de vie. Les différents phénotypes douloureux (douleurs musculosquelettiques, fatigue chronique, dépression) ainsi que la morbidité secondaire et le recours aux soins ont été également mesurés. Parmi les 386 sujets répondants, les 193 sujets infectés par le CHIKV ne présentaient pas davantage de douleurs musculosquelettiques, de fatigue ou de dépression que les 193 sujets non infectés à 10–11 ans de l'exposition initiale. Le score PCS moyen était de 66,6 (± 21,6) chez les infectés et de 71,0 (± 19,7) chez les non-infectés (p = 0,06). Aucune dimension de la qualité de vie n'était significativement altérée chez les sujets infectés par rapport aux sujets non infectés. Les sujets infectés n'ont pas développé davantage de diabète de type 2, de cancer ou d'autres maladies connues que les sujets non infectés. Parmi les sujets douloureux, les sujets infectés n'ont pas davantage nécessité un recours aux rhumatologues, à des neurologues ou à d'autres médecins spécialistes. À dix ans d'une épidémie de Chikungunyna, les sujets infectés ne présentent pas plus de morbidités que les sujets non infectés, et leur qualité de vie est sensiblement identique. Ces résultats préliminaires contrastent fortement avec ceux acquis à deux ans de l'épidémie et avec tous les résultats obtenus sur des populations hospitalières ou des populations sélectionnées par la gravité initiale. Ils rassurent à distance sur le caractère bénin de cette maladie.

Background: Little is known about the neurocognitive outcome in children exposed to perinatal mother-to-child Chikungunya virus (p-CHIKV) infection.Methods: The CHIMERE ambispective cohort study compared the neurocognitive function of 33 p-CHIKV-infected children (all but one enrolled retrospectively) at around two years of age with 135 uninfected peers (all enrolled prospectively). Psychomotor development was assessed using the revised Brunet-Lezine scale, examiners blinded to infectious status. Development quotients (DQ) with subscores covering movement/posture, coordination, language, sociability skills were calculated. Predictors of global neurodevelopmental delay (GND, DQ <= 85), were investigated using multivariate Poisson regression modeling. Neuroradiologic follow-up using magnetic resonance imaging (MRI) scans was proposed for most of the children with severe forms.Results: The mean DQ score was 86.3 (95% CI: 81.0-91.5) in infected children compared to 100.2 (95% CI: 98.0-102.5) in uninfected peers (P<0.001). Fifty-one percent (n = 17) of infected children had a GND compared to 15% (n = 21) of uninfected children (P<0.001). Specific neurocognitive delays in p-CHIKV-infected children were as follows: coordination and language (57%), sociability (36%), movement/posture (27%). After adjustment for maternal social situation, small for gestational age, and head circumference, p-CHIKV infection was found associated with GND (incidence rate ratio: 2.79, 95% CI: 1.45-5.34). Further adjustments on gestational age or breastfeeding did not change the independent effect of CHIKV infection on neurocognitive outcome. The mean DQ of p-CHIKV-infected children was lower in severe encephalopathic children than in non-severe children (77.6 versus 91.2, P < 0.001). Of the 12 cases of CHIKV neonatal encephalopathy, five developed a microcephaly (head circumference < -2 standard deviations) and four matched the definition of cerebral palsy. MRI scans showed severe restrictions of white matter areas, predominant in the frontal lobes in these children.Conclusions: The neurocognitive outcome of children exposed to perinatal mother-to-child CHIKV infection is poor. Severe CHIKV neonatal encephalopathy is associated with an even poorer outcome.

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.

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≥15 years) having declared RMSP at disease onset were extracted from the TELECHIK cohort study, Reunion island, and analyzed 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 for 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.

ObjectiveThe aim of the present study was to weigh up, at the community level, the respective roles played by pandemic Influenza (pH1N1) virus and co-circulating human Non-Influenza Respiratory Viruses (NIRVs) during the first wave of the 2009 pH1N1 pandemic.MethodsA population-based prospective cohort study was conducted in Reunion Island during the austral winter 2009 (weeks 30-44) that allowed identification of 125 households with at least one member who developed symptoms of Influenza-like illness (ILI). Three consecutive nasal swabs were collected from each household member (443 individuals) on day 0, 3 and 8 post-ILI report and tested for pH1N1 and 15 NIRVs by RT-PCR.ResultsTwo successive waves of viral infections were identified: a first wave (W33-37) when pH1N1 was dominant and co-circulated with NIRVs, sharply interrupted by a second wave (W38-44), almost exclusively composed of NIRVs, mainly human Rhinoviruses (hRV) and Coronaviruses (hCoV). Data suggest that some interference may occur between NIRVs and pH1N1 when they co-circulate within the same household, where NIRVs were more likely to infect pH1N1 negative individuals than pH1N1 positive peers (relative risk: 3.13, 95% CI: 1.80-5.46, P<0.001). Viral shedding was significantly shorter (P = 0.035) in patients who were co-infected by pH1N1 and NIRV or by two different NIRVs compared to those who were infected with only one virus, whatever this virus was (pH1N1 or NIRVs). Although intense co-circulation of NIRVs (especially hRV) likely brought pH1N1 under the detection threshold, it did not prevent spread of the pandemic Influenza virus within the susceptible population nor induction of an extensive herd immunity to it.ConclusionOur results suggest that NIRV co-infections during Influenza epidemics may act as cofactors that contribute to shape an outbreak and modulate the attack rate. They further warrant broad spectrum studies to fully understand viral epidemics.

BACKGROUND: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.METHODS: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.RESULTS: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.CONCLUSION: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.

BACKGROUND:Persistent disabilities are key manifestations of Chikungunya virus (CHIKV) infection, especially incapacitating polyarthralgia and fatigue. So far, little is known about their impact on health status. The present study aimed at describing the burden of CHIKV prolonged or late-onset symptoms on the self-perceived health of La Réunion islanders.METHODS:At 18 months after an outbreak of Chikungunya virus, we implemented the TELECHIK survey; a retrospective cohort study conducted on a random sample of the representative SEROCHIK population-based survey. A total of 1,094 subjects sampled for CHIKV-specific IgG antibodies in the setting of La Réunion island in the Indian Ocean, between August 2006 and October 2006, were interviewed about current symptoms divided into musculoskeletal/rheumatic, fatigue, cerebral, sensorineural, digestive and dermatological categories.RESULTS:At the time of interview, 43% of seropositive (CHIK+) subjects reported musculoskeletal pain (vs 17% of seronegative (CHIK-) subjects, P < 0.001), 54% fatigue (vs 46%, P = 0.04), 75% cerebral disorders (vs 57%, P < 0.001), 49% sensorineural impairments (vs 37%, P = 0.001), 18% digestive complaints (vs 15%, P = 0.21), and 36% skin involvement (vs 34%, P = 0.20) on average 2 years after infection (range: 15-34 months). After controlling for confounders such as age, gender, body mass index or major comorbidities in different Poisson regression models, 33% of joint pains were attributable to CHIKV, 10% of cerebral disorders and 7.5% of sensorineural impairments, while Chikungunya did not enhance fatigue states, digestive and skin disorders.CONCLUSIONS:On average, 2 years after infection 43% to 75% of infected people reported prolonged or late-onset symptoms highly attributable to CHIKV. These manifestations carry a significant burden in the community in the fields of rheumatology, neurology and sensorineural health.

BACKGROUND:To date, there is little information that reflects the true extent of spread of the pH1N1/2009v influenza pandemic at the community level as infection often results in mild or no clinical symptoms. This study aimed at assessing through a prospective study, the attack rate of pH1N1/2009 virus in Reunion Island and risk factors of infection, during the 2009 season.METHODOLOGY/PRINCIPAL FINDINGS:A serosurvey was conducted during the 2009 austral winter, in the frame of a prospective population study. Pairs of sera were collected from 1687 individuals belonging to 772 households, during and after passage of the pandemic wave. Antibodies to pH1N1/2009v were titered using the hemagglutination inhibition assay (HIA) with titers ≥ 1/40 being considered positive. Seroprevalence during the first two weeks of detection of pH1N1/2009v in Reunion Island was 29.8% in people under 20 years of age, 35.6% in adults (20-59 years) and 73.3% in the elderly (≥ 60 years) (P<0.0001). Baseline corrected cumulative incidence rates, were 42.9%, 13.9% and 0% in these age groups respectively (P<0.0001). A significant decline in antibody titers occurred soon after the passage of the epidemic wave. Seroconversion rates to pH1N1/2009 correlated negatively with age: 63.2%, 39.4% and 16.7%, in each age group respectively (P<0.0001). Seroconversion occurred in 65.2% of individuals who were seronegative at inclusion compared to 6.8% in those who were initially seropositive.CONCLUSIONS:Seroincidence of pH1N1/2009v infection was three times that estimated from clinical surveillance, indicating that almost two thirds of infections occurring at the community level have escaped medical detection. People under 20 years of age were the most affected group. Pre-epidemic titers ≥ 1/40 prevented seroconversion and are likely protective against infection. A concern was raised about the long term stability of the antibody responses.

En mars 2009, un nouveau virus Influenza A a emerge au Mexique et aux Etats-Unis, caracterise par une combinaison de segments genomiques d'origines humaine, porcine et aviaire. La diffusion tres rapide de ce virus au reste du monde a specifie la 1ere pandemie grippale du 21eme siecle. Le 1er cas confirme a La Reunion, chez un voyageur en provenance d'Australie, date du 5 juillet 2009. Des le 21 Juillet 2009, date du premier cas a transmission indigene rapporte par La CIRE-Reunion- Mayotte, le CRVOI et le CIC-EC de La Reunion ont lance une enquete prospective en cohorte populationnelle, le programme CoPanFlu-Run. Son objectif est de decrire l'histoire naturelle de l'infection en population generale ainsi que mesurer les parametres epidemiologiques, virologiques et sociologiques de l'epidemie. L'etude serologique a revele que La Reunion a ete fortement impactee par l'epidemie grippale, surtout chez les enfants d'âge scolaire : pres de 63% des moins de 20 ans ont seroconverti, un peu moins de 40% pour la tranche d'âge 20-59 ans, et 16,7% pour les plus de 60 ans. Compares a l'estimation de la CIRE-Reunion-Mayotte qui annonce un taux d'attaque de 12.5% de formes symptomatiques ayant eu recours aux services sanitaires, ces resultats montrent la grande diffusion de l'epidemie sous forme peu ou pas symptomatique et sa grande benignite a l'echelle communautaire. Notre etude montre par ailleurs que les taux d'anticorps au 1/40 cross reactants avec le virus pandemique presents eventuellement avant le passage epidemique protegent contre la seroconversion. L'etude virologique, a permis de detecter le virus pandemique dans les prelevements nasaux de 71 individus dont la plupart etaient symptomatiques. Elle a en outre mis en evidence l'existence d'une co-circulation d'autres virus respiratoires (essentiellement rhinovirus et coronavirus) en population generale avant, pendant, et apres le passage de la vague epidemique. Le sequencage de 28 souches de virus H1N1p 2009 detectees au sein de notre cohorte reunionnaise, a permis leur analyse phylogenetique. Les souches reunionnaises, bien qu'issues du clade 7 au niveau mondial, dans lequel, on retrouve les souches indiennes, australiennes et japonaises, forment un clade a part entiere. Par ailleurs, il semble que l'origine des souches analysees n'est vraisemblablement pas australienne comme supposee au depart de l'epidemie, et qu'au moins 2 introductions concomitantes se sont produites a La Reunion. La premiere datant du 26 juin 2009, c'est-a-dire, 1 mois avant la datation de la circulation virale active estimee par la CIRE, et la seconde datant du 8 juillet 2009. Finalement, une fois que la vague epidemique en population s'est eteinte en moins de 9 semaines, l'etude du cheptel porcin a montre un passage substantiel chez l'animal qui se maintient jusqu'a ce jour. (Texte integral)