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Objectives To investigate whether the lactate dehydrogenase D (LDHD) gene deficiency causes juvenile-onset gout. Methods We used whole-exome sequencing for two families and a targeted gene-sequencing panel for an isolated patient. d-lactate dosages were analysed using ELISA. Results We demonstrated linkage of juvenile-onset gout to homozygous carriage of three rare distinct LDHD variants in three different ethnicities. In a Melanesian family, the variant was (NM_153486.3: c.206C>T; rs1035398551) and, as compared with non-homozygotes, homozygotes had higher hyperuricaemia (P = 0.02), lower fractional clearance of urate (P = 0.002), and higher levels of d-lactate in blood (P = 0.04) and urine (P = 0.06). In a second, Vietnamese, family, very severe juvenile-onset gout was linked to homozygote carriage of an undescribed LDHD variant (NM_153486.3: c.1363dupG) leading to a frameshift followed by a stop codon, p.(AlaGly432fsTer58). Finally, a Moroccan man, with early-onset and high d-lactaturia, whose family was unavailable for testing, was homozygous for another rare LDHD variant [NM_153486.3: c.752C>T, p.(Thr251Met)]. Conclusion Rare, damaging LDHD variants can cause autosomal recessive early-onset gout, the diagnosis of which can be suspected by measuring high d-lactate levels in the blood and/or urine.

Antibacterial activity of Xylopia pancheri Baill. (Annonaceae) leaf extract was investigated against susceptible Staphylococcus aureus, methicillin-resistant S. aureus (MRSA) and extended-spectrum-β-lactamase (ESBL)-producing Pseudomonas aeruginosa. Results showed that X. pancheri leaf extract displayed antibacterial activity against S. aureus with higher inhibitory effect on MRSA compared to control gentamycin antibiotic, and IC

ObjectivesAn increasing number of isolations ofCorynebacterium diphtheriaehas been observed in recent years in the archipelago of New Caledonia. We aimed to analyze the clinical and microbiological features of samples withC. diphtheriae.MethodsAllC. diphtheriaeisolates identified in New Caledonia from May 2015 to May 2019 were included. For each case, a retrospective consultation of the patient files was conducted. Antimicrobial susceptibility phenotypes,toxgene and diphtheria toxin expression, biovar and the genomic sequence were determined. Core genome multilocus sequence typing (cgMLST), 7-gene MLST and search of genes of interest were performed from genomic assemblies.Results58 isolates were included, with a median age of patients of 28 years (range: 9 days to 78 years). Cutaneous origin accounted for 51 of 58 (87.9%) isolates, andC. diphtheriaewas associated withStaphylococcus aureusand/orStreptococcus pyogenesin three quarters of cases. Half of cases came either from the main city Noumea (24%, 14/58) or from the sparsely populated island of Lifou (26%, 15/58). Six tox-positive isolates were identified, associated with recent travel to Vanuatu; 5 of these cases were linked and cgMLST confirmed recent transmission. Two cases of endocarditis in young female patients with a history of rheumatic fever involved tox-negative isolates. The 58 isolates were mostly susceptible to commonly used antibiotics. In particular, no isolate was resistant to the first-line molecules amoxicillin or erythromycin. Resistance to tetracycline was found in a genomic cluster of 17 (29%) isolates, 16 of which carried thetetOgene. There were 13 cgMLST sublineages, most of which were also observed in the neighboring country Australia.ConclusionsCutaneous infections may harbor non-toxigenicC. diphtheriaeisolates, which circulate largely silently in non-specific wounds. The possible introduction of tox-positive strains from a neighboring island illustrates that diphtheria surveillance should be maintained in New Caledonia, and that immunization in neighboring islands must be improved. Genomic sequencing uncovers how genotypes circulate locally and across neighboring countries.

Leptospirosis is endemic in New Caledonia. Clinical diagnosis is often difficult and its evolution can be fatal. Leptospirosis requires specific management before biological confirmation. Modified Faine criteria (Faine Score) have been suggested to diagnose leptospirosis on epidemiological (parts A and B) and biological (part C) criteria. The main objective of our study was to assess the relevance of the epidemiological–clinical modified Faine score, parts A and B (MF A + B), in patients with suspected leptospirosis in New Caledonia. A monocentric case–control study was conducted in suspect patients for whom a Leptospira polymerase chain reaction (PCR) test was done within the first 7 days of signs onset at the tertiary hospital from January 2018 to January 2019. Cases and control subjects were matched 1:2 in the gender and age categories. Bivariate, and then multivariable, analyses studied the association between the MF A + B score and a positive Leptospira PCR test, adjusted on the variables retained. In all, 35 cases and 70 control subjects matched for age and gender were analyzed. Multivariable analysis by logistic regression found a significant association between an MF A + B score taken from the categories “possible leptospirosis” (score, 20–25) and “presumed leptospirosis” (score, > 26), and the case or control subject status (P < 0.0001). Model performance was high, with an area under the curve value of 99.27%, 93.55% sensitivity, and 96.36% specificity, which classified subjects correctly in 95.35% of cases. Our study suggests using the MF A + B score to identify possible cases of leptospirosis and initiate antibiotic therapy before biological confirmation in New Caledonia. This score should be evaluated in areas where more differential diagnoses exist and where PCR is not widely available.

The mosquito Aedes aegypti is the major vector of arboviruses like dengue, Zika and chikungunya viruses. Attempts to reduce arboviruses emergence focusing on Ae. aegypti control has proven challenging due to the increase of insecticide resistances. An emerging strategy which consists of releasing Ae. aegypti artificially infected with Wolbachia in natural mosquito populations is currently being developed. The monitoring of Wolbachia-positive Ae. aegypti in the field is performed in order to ensure the program effectiveness. Here, the reliability of the Matrix‑Assisted Laser Desorption Ionization‑Time Of Flight (MALDI‑TOF) coupled with the machine learning methods like Convolutional Neural Network (CNN) to detect Wolbachia in field Ae. aegypti was assessed for the first time. For this purpose, laboratory reared and field Ae. aegypti were analyzed. The results showed that the CNN recognized Ae. aegypti spectral patterns associated with Wolbachia-infection. The MALDI-TOF coupled with the CNN (sensitivity = 93%, specificity = 99%, accuracy = 97%) was more efficient than the loop-mediated isothermal amplification (LAMP), and as efficient as qPCR for Wolbachia detection. It therefore represents an interesting method to evaluate the prevalence of Wolbachia in field Ae. aegypti mosquitoes.

Background Hemotropic mycoplasmas, previously classified in the genus Eperythrozoon, have been reported as causing human infections in Brazil, China, Japan, and Spain. Methods In 2017, we detected DNA from Candidatus Mycoplasma haemohominis in the blood of a Melanesian patient from New Caledonia presenting with febrile splenomegaly, weight loss, life-threatening autoimmune hemolytic anemia, and hemophagocytosis. The full genome of the bacterium was sequenced from a blood isolate. Subsequently, we retrospectively (2011–2017) and prospectively (2018–2019) tested patients who had been hospitalized with a similar clinico-biological picture. In addition, as these patients had been in contact with frugivorous bats (authorized under conditions for hunting and eating in New Caledonia), we investigated the role of these animals and their biting flies by testing them for hemotropic mycoplasmas. Results There were 15 patients found to be infected by this hemotropic mycoplasma. Among them, 4 (27%) died following splenectomy performed either for spontaneous spleen rupture or to cure refractory autoimmune hemolytic anemia. The bacterium was cultivated from the patient’s blood. The full genome of the Neocaledonian Candidatus M. haemohominis strain differed from that of a recently identified Japanese strain. Of 40 tested Pteropus bats, 40% were positive; 100% of collected bat flies Cyclopodia horsfieldi (Nycteribiidae, Diptera) were positive. Human, bat, and dipteran strains were highly similar. Conclusions The bacterium being widely distributed in bats, Candidatus M. haemohominis, should be regarded as a potential cause of severe infections in humans.

International audience; ObjectiveCarbapenemase-producing Enterobacteriaceae (CRE) and Enterococcus faecium resistant to vancomycin (VRE) constitute major threats to public health worldwide. The Pacific area is concerned and has implemented strategies to control antimicrobial resistance (AMR). However, accurate epidemiological data are rarely reported. Our study aimed to present the strategies applied to prevent and control the spread of highly resistant bacteria in the Pacific territory of New Caledonia.Patients and methodsCohort prospective study of all cases of highly resistant bacteria (HRB) isolated in New Caledonia from September 2004 to December 2020. Evaluation of the impact of the infection control measures implemented in healthcare settings: screening strategy, cohorting unit, IT tools and control of antibiotic prescriptions.ResultsA total of 346 patients with HRB were identified. Most of them (63.0%) were infected or colonized by VRE (n = 218) and 128 by CRE. While the number of CREs significantly increased from 2013 to 2020 (P < 0.0001), control procedures have limited their dissemination. Most patients were colonized by IMP-4-CRE (n = 124/128). The incidence density of VRE significantly decreased from 38.52 for 100,000 hospitalisation-days in 2015 to 4.19 for 100,000 hospitalisation-days in 2019 due to systematic screening of patients before sanitary repatriation from Australia and cohorting implementation. The risk of VRE diffusion is now well under control.ConclusionsOur study confirms that it is possible to control the spread of AMR in a circumscribed territory by means of a global control strategy involving screening, cohorting unit, IT tools and antibiotic prescription controls.

Introduction L’antibioresistance est une preoccupation majeure de nos jours. En Nouvelle-Caledonie, la prevalence du SARM-Communautaire progresse depuis plusieurs annees sans que nous en ayons l’explication. En 2018, le taux de SARM atteint 40,1 %. Nous emettons l’hypothese que la prise en charge inadaptee des infections cutanees, largement liees a ce pathogene, pourrait en etre une des causes, notamment dans la surconsommation d’antibiotiques. Nous nous sommes ainsi interesses aux pratiques des medecins face a ces infections, notamment concernant les soins locaux, la documentation microbiologique, l’antibiotherapie et la decolonisation. Materiels et methodes Il s’agit d’une etude descriptive transversale des pratiques declarees par auto-questionnaire des medecins caledoniens en soins primaires en fevrier et mars 2020. Les reponses sont analysees en fonction des recommandations nationales de 2019 HAS/SPILF/SDF et de l’ecologie locale. Resultats On constate globalement un mesusage des antibiotiques. Dans les formes peu severes d’impetigo et de furoncle, pour lesquelles un traitement local est suffisant, une antibiotherapie orale est prescrite respectivement par 22 % (18/80) et 27 % (22/80) des praticiens. Lorsqu’un antibiotique oral est indique, comme dans le furoncle complique et l’abces, les durees de prescription sont trop longues, respectivement, dans 87,5 % (64/79) et 82 % (56/68) des cas. L’amoxicilline–acide clavulanique est prescrit par 32,5 % (26/79) a 42 % (29/69) des medecins selon les tableaux cliniques chez l’adulte. Chez l’enfant, cette prescription atteint 74% (59/80) dans le furoncle complique. L’acide fusidique topique est utilise dans 32% (21/65) des impetigos peu severes. Ces deux antibiotiques sont pourtant inadaptes a l’ecologie locale au vu de leur taux de resistance eleve sur le territoire. La documentation microbiologique est peu effectuee. Elle est demandee dans 15 % (12/80) des impetigos severes, 20 % (20/80) des abces et 28 % (22/79) des furoncles compliques. La decolonisation est mal connue. Elle est prescrite pendant la poussee par 35 % (31/69) des medecins. Seulement 32 % (22/69) inclus le patient et son entourage dans le protocole. On constate un oubli du gite oral dans 69 % (47/68) des cas. Le taux de SARM est sous-estime par 40,5 % (30/74) des medecins du territoire. Soixante-quatre pour cent (51/80) d’entre eux voient au moins une lesion d’infection cutanee par jour en consultation. Dans les provinces du Nord et des Iles Loyaute, ou la majorite de la population vit en tribu, cette frequence s’eleve a 91 % (30/33). Conclusion Ces pratiques inappropriees associees a la presence d’un clone de SARM bien adapte a son environnement et a une frequence particulierement elevee des infections cutanees, participent probablement a la propagation du SARM sur le territoire. Pour lutter contre ce phenomene, une communication efficace entre les professionnels de sante, les autorites sanitaires et la population ainsi qu’une meilleure prevention collective de ces infections sont indispensables.

Introduction Eosinophilic meningitis is a rare form of meningitis with sequelae or death occurring in approximately 2–3% of cases. The most frequent etiological agent is the parasite Angiostrongylus cantonensis. The aim of this study was to characterize New Caledonian cases and to assess the extent to which of A. cantonensis was involved. Material and methods We performed a retrospective study of all cases of eosinophilic meningitis (EM) admitted to the Territorial Hospital of New Caledonia, from 2004 to 2019. We performed a descriptive and a multivariate analysis to identify association of variables with severe and fatal cases (or cases with sequelae). Conclusion Angiostrongyliasis was confirmed as being responsible for 17 of the 92 reported EM cases in New Caledonia from 2004 to 2019 with most being young adults and non-walking infants, and with two peaks of incidence one during the dry season and one during the rainy season. Considering the high incidence and regularity of cases, the potential reservoirs should be identified to target prevention campaigns.

This work was presented at the following congresses: SFRA, September 2017 and SRLF, January 2018; International audience; Introduction: Hypermucoviscous Klebsiella pneumoniae (KP) strains are responsible for complicated bacteremia with multiple septic sites (liver, central nervous system, muscles). We aimed to compare the clinical severity of patients presenting with KP bacteremia based on the hypermucoviscous or non-hypermucoviscous characteristic of the strains.Methods: Observational retrospective study successively including all patients with KP bacteremia from May 2013 to March 2015 at the tertiary medical center of New Caledonia. The hypermucoviscous characteristic was defined by the string test results and molecular analysis to determine the capsular serotype.Results: A total of 55 bacteremic patients were included in the study; 27% of isolated strains were hypermucoviscous. Hypermucoviscous strains accounted for two-thirds of community-acquired infections (72.5% vs. 33.4%, p=0.01). The rate of intensive care hospitalization was high (hypermucoviscous 46.7%; standard 52.5%) without any difference between the two groups. No significant difference was observed in case fatality (hypermucoviscous 46.7% vs. standard 15%, p=0.07) but patients with hypermucoviscous strains had longer hospital stays (73.5 days versus 50.7 days, p=0.04) and longer persistence of positive blood cultures despite an appropriate treatment (OR 1.41, 95% CI: 1.0-1.96, p=0.045).Conclusion: Hypermucoviscous KP bacteremia account for most community-acquired Klebsiella infections in New Caledonia and are associated with longer hospital stay and persistence of positive blood cultures despite the implementation of an appropriate treatment.

International audience; With the increasing use of real time PCR techniques, Leptospira isolation has mostly been abandoned for the diagnosis of human leptospirosis. However, there is a great value of collecting Leptospira isolates to better understand the epidemiology of this complex zoonosis and to provide the researchers with different isolates. In this study, we have successfully isolated different Leptospira strains from BacT/Alert aerobic blood culture bottles and suggest that this privileged biological material offers an opportunity to isolate leptospires.

Introduction La lepre a ete signalee sur ce territoire depuis le 19e siecle et persiste encore aujourd’hui. La decouverte de nouveaux cas repose sur un depistage passif, par les medecins de ville ou de dispensaire, des patients qui sont ensuite adresses au Centre Hospitalier Territorial et sur un depistage actif des personnes contacts des nouveaux cas qui sont suivies pendant 5 ans. La surveillance active de la lepre sur ce territoire au cours des 6 dernieres annees montre un taux d’incidence global inferieur au seuil fixe par l’OMS (1/10 000 habitants). Cependant, il persiste une zone d’endemicite sur un petit archipel isole (lieu de la 1ere leproserie sur ce territoire) ou l’incidence est de 16,1/10 000. Dans cette commune, entre 2015 et 2017, 4 enfants dont un de 2 ans ont ete diagnostiques, ce qui demontre une circulation active de la maladie. Materiels et methodes L’enquete visait l’ensemble de la population de cet archipel (843 habitants), ainsi que les personnes presentes au moment de la campagne de depistage. Apres signature du consentement, un questionnaire standardise permettait de recueillir des donnees sur les caracteristiques sociodemographiques (âge, sexe, tribu), les antecedents de lepre ou de contact avec un patient lepreux et d’eventuels symptomes. Un examen clinique ainsi que 3 prelevements ont ete realises a la fin de l’entrevue : un prelevement du suc dermique des 2 lobes d’oreille, le frottis de la muqueuse nasale pour analyse microbiologique et PCR ainsi qu’un prelevement de sang capillaire pour test immunologique. Resultats Au total, 621 personnes ont participe au depistage (74 % de la population globale). Sur les 621, 597 ont eu un prelevement du suc dermique, 610 un prelevement du mucus nasal et un prelevement de sang capillaire. A l’issue du depistage clinique, 8 cas probables de lepre ont ete diagnostiques (presence de tache (s) hypochrome(s) et hypoesthesique(s)) ayant eu chacun 1 biopsie, dont 5 ayant moins de 18 ans. Cinq de ces 8 cas suspects ont ete confirmes et necessitent un traitement (lepre paucibacillaire). Trois cent une personnes ont declare avoir ou avoir eu un cas de lepre dans leur entourage, soit 48,5 % de la population. Conclusion Pour la premiere fois, une enquete exhaustive de depistage de la lepre avec recherche d’eventuels porteurs asymptomatiques a ete realisee sur une population isolee de ce territoire. Cette enquete a ete un succes et a permis de confirmer une circulation active de la maladie notamment chez les jeunes. Elle a egalement permis de mettre en evidence la necessite d’une recherche active de cas. Enfin, l’exposition de pres de la moitie de la population a la maladie amene les autorites sanitaires a envisager le traitement de l’ensemble de cette population insulaire.

Introduction Depuis 1990, nous observons en Nouvelle-Caledonie un tableau clinique associant splenomegalie febrile et amaigrissement, anemie hemolytique auto-immune (AHAI) et/ou lymphohistiocytose hemophagocytaire (HLH) chez des patients ayant ete en contact avec des roussettes (chauves-souris frugivores). Une etiologie infectieuse est suspectee mais aucun micro-organisme n’est mis en evidence. Devant la suspicion d’une infection a bacterie de culture fastidieuse, le sang d’une patiente presentant ce tableau a ete investigue et une PCR ciblant le gene de l’ARN16S retrouve candidatus Mycoplasma haemohominis. Il s’agit d’une bacterie intracellulaire jamais cultivee appartenant au groupe des Hemoplasma, decrite chez les animaux y compris des chauves-souris. Un seul cas humain a ete rapporte en 2011 chez une anglaise ayant voyage (Australie, Singapour). Nous rapportons la premiere serie de cas humains et avons identifie les roussettes comme reservoir animal local. Materiels et methodes Suite a la description du cas index, nous avons mene une etude retrospective (patients suspects hospitalises 2009–2017, registre territorial de HLH 2012–2018) et prospective (2018). Le sang de 10 patients, la rate et l’encephale de 40 roussettes ont ete investigues par 2 systemes de qPCR et PCR standard ciblant les genes de l’ARN16S et dnaK de M. haemohominis. Resultats Dix cas humains ont ete identifies. Ces patients n’avaient pas de lien epidemiologique mais 9 rapportaient un contact recent avec des roussettes. Tous presentaient amaigrissement, fievre prolongee et splenomegalie, syndrome inflammatoire, hypergammaglobulinemie polyclonale et plasmocytose medullaire reactionnelle. Une AHAI a anticorps chauds etait presente dans 9 cas et une HLH dans 9 cas. L’ADN bacterien a ete detecte (sang peripherique et/ou medullaire) par les 2 qPCR chez 10 patients et confirme par sequencage chez 4 patients. Une antibiotherapie par doxycycline a ete efficace dans 7/10 cas. Trois patients sont decedes suite a une rupture spontanee de rate (n = 2) ou apres splenectomie (n = 1). Trois especes de roussette du genre Pteropus (ornatus, vetulus et tonganus) ont ete collectees. L’ADN de candidatus M. haemohominis a ete detecte chez 52,5 % (21/40) d’entre-elles. Conclusion Nous decrivons une nouvelle zoonose responsable d’AHAI et/ou HLH d’evolution potentiellement fatale. La mise en route rapide d’une antibiotherapie probabiliste par doxycycline pourrait ameliorer le pronostic. Des investigations complementaires sont en cours pour comprendre les modes de transmission de cette bacterie. Les resultats preliminaires des cultures bacteriennes sont prometteurs et permettront prochainement d’obtenir son genome.

Summary Background Little data on the usefulness of microbiological samples in appendicular peritonitis (AP) are available. The objectives of the study were to document the clinical value of systematic peritoneal swabbing in complicated appendicitis, to establish whether they influence postoperative outcome, and to help to optimize empirical preoperative treatment. Methods Charts of all consecutive patients undergoing appendicectomy for acute perforated appendicitis were analyzed over a 7-year period from 2005 to 2011 in a tertiary hospital in New Caledonia. From prospectively recorded data, microbiological culture results, and sensitivity of isolates were obtained in relation to histopathological findings and infective morbidity. Results Overall, 144 cases including 47 (33%) children and 97 (67%) adults with perforated appendicitis were included in the study. Fifty-one (35%) had generalized peritonitis treated laparoscopically in 30 (59%) cases. Peritoneal fluid samples yielded a positive culture in 104 (74%) patients. The most commonly recovered species were Escherichia coli (81%), Streptococcus milleri group (12%), and Pseudomonas aeruginosa (12%). Postoperative infectious complications occurred in 32 (22%) including intra-abdominal abscess ( n = 20) and wound infection ( n = 12). Probabilist antibiotic regimen was less often suitable in children than in adults ( p = 0.003). Infectious complications occurred more often in cases with an unsuitable antibiotic regimen after culture results compared with a suitable antibiotic regimen before culture results ( p = 0.01). Conclusion Although antibiotic use may be considered as an adjunct to surgical intervention of AP, the appropriate use of preoperative antibiotics and modifications according to culture results are essential to prevent infectious complications.

Introduction La lepre, maladie chronique causee par Mycobacterium leprae ou bacille de Hansen, a ete signalee sur ce territoire d’environ 270 000 habitants des le 19e siecle et persiste encore aujourd’hui. La premiere leproserie, installee sur l’Ile de B. de 1892 a 1898, a abrite jusqu’a 500 lepreux. La decouverte de nouveaux cas repose aujourd’hui soit sur un depistage actif des sujets contacts qui sont suivis pendant environ 5 ans ; soit passivement, la majorite des patients etant adressee au service de medecine interne, par leur medecin traitant ou le dispensaire dont ils dependent. Materiels et methodes Sur ce territoire la lepre est une maladie a declaration obligatoire depuis 1986. L’analyse presentee est basee sur le registre national de la lepre qui couvre les 35 dernieres annees d’enregistrement. Le diagnostic des cas est microscopique (anatomopathologie, coloration de Ziehl, et/ou PCR) sur le mucus nasal et le suc dermique des oreilles ainsi que les biopsies d’eventuelles lesions cutanees. Les formes multibacillaires (MB) sont adressees au CNR pour la recherche de chimioresistance. Le traitement comporte une polychimiotherapie (PC) selon les recommandations de l’OMS. Resultats De 1983 a 2017, 342 patients ont ete enregistres dont 225 hommes, 115 femmes et 2 non renseignes. La majorite des cas avait entre 25 et 50 ans. La proportion de nouveaux cas avec une forme MB est elevee : 57,6 % au cours des 10 dernieres annees. L’introduction de la PC, il y a 30 ans, a ete suivie d’une diminution considerable du nombre de nouveaux cas. Sur les 10 dernieres annees, l’incidence oscille entre 0,37 et 3,92 cas/100000 habitants ; la fluctuation etant liee au faible nombre de nouveaux cas annuels (1 a 10). Une fraction de ces diagnostics est constituee de rechutes : 1 en 2011 (9,1 %), 2 en 2012 (28,6 %), 2 en 2013 (25 %, souches sensibles aux anti-lepreux), aucun de 2014 a 2016 et 1 en 2017. Depuis 1996, la prevalence de la maladie se maintient a un niveau inferieur au seuil d’endemicite fixe a 1/10000 habitants par l’OMS, sauf pour 3 communes. La plus touchee est B. avec une prevalence 4,5 fois superieure a ce seuil. Parmi les 12 nouveaux cas detectes sur cette commune depuis 10 ans, 5 etaient des enfants dont un âge de 3 ans, ce qui demontre une circulation active du bacille. Conclusion Les resultats de la surveillance active de la lepre montrent une persistance de l’endemicite de cette maladie avec une surincidence sur l’ile de B. Aussi, une campagne de depistage exhaustive de la population de cette commune sera realisee en 2018 afin de rechercher de nouveaux cas et d’essayer d’identifier des causes de la persistance de la transmission de la lepre. Ce projet entre dans le cadre de la Strategie mondiale de la lutte contre la lepre lancee le 20 avril 2016 et la Declaration de Bangkok de 2013.

Introduction La lymphohistiocytose hemophagocytaire (HLH) de l’adulte est le plus souvent d’origine infectieuse, inflammatoire ou tumorale. La letalite varie de 20,4 % a 43,4 % selon les series. La « fievre hemolytique des roussettes » est une zoonose recemment decrite en milieu tropical, souvent responsable d’HLH et d’anemie hemolytique auto-immune (AHAI). L’infection est due a une nouvelle bacterie intracellulaire, Mycoplasma haemohominis caledoniensis, dont le seul reservoir identifie est la chauve-souris. Nous decrivons une cohorte de HLH en milieu tropical. Materiels et methodes Les dossiers des patients adultes hospitalises entre janvier 2012 et decembre 2018, presentant une ferritinemie ≥ 2000 μg/L et/ou une hemophagocytose medullaire, ont ete etudies retrospectivement. Le critere d’inclusion etait un H-score ≥ 170. L’infection a Mycoplasma haemohominis caledoniensis a ete recherchee par PCR chez les patients sans cause identifiee. Resultats Parmi les 495 dossiers analyses, 90 patients ont ete inclus. L’âge moyen etait 50,4 ans, le ratio H/F de 1/1,1. Vingt-six patients (28,9 %) presentaient plus d’un facteur declenchant et 118 facteurs ont ete pris en compte. Il s’agissait d’une infection dans 44,1 % des cas (33 bacteriennes, 14 virales, 5 fongiques), d’une hemopathie dans 22,9 % (27 dont 20 lymphomes), d’une maladie auto-immune dans 14,4 % (17), d’un cancer solide dans 7,6 % (9), d’un medicament dans 4,3 % (5) et d’une forme familiale dans 0,8 % (1). Pour 7,8 % des patients (7) la cause n’a pas ete retrouvee. Une « fievre hemolytique des roussettes » a ete identifiee chez 9 patients (10 %). Mycoplasma haemohominis caledoniensis (9) etait le premier agent infectieux (17,3 %) suivi par 8 infections a Pseudomonas aeruginosa(15,4 %), 8 a CMV (15,4 %) et 4 a Mycobacterium tuberculosis (7,7 %). Tous les patients avaient de la fievre et 64,4 % une splenomegalie (32). Une hemolyse etait presente dans 18,9 % des cas (17). Cinquante patients (55,5 %) ont recu une corticotherapie et 4 (4,4 %) de l’etoposide. La letalite a 30 jours etait de 25,5 % (23) parmi les HLH et de 33,3 % (3) parmi les infections a Mycoplasma haemohominis caledoniensis. La doxycycline, lorsqu’elle a ete utilisee dans les infections a Mycoplasma haemohominis caledoniensis, a permis la guerison (6). Conclusion Notre cohorte d’HLH adultes differe de celles menees dans des zones non tropicales par la forte proportion d’infections bacteriennes non tuberculeuses. La « fievre hemolytique des roussettes » etait responsable de 10 % des cas d’HLH. Cette infection letale doit etre recherchee par PCR Mycoplasma haemohominis caledoniensis dans le sang et la moelle des patients avec une splenomegalie febrile associee a une HLH et/ou AHAI dans les regions d’Asie-Pacifique et l’Ocean Indien. Une antibiotherapie probabiliste par doxycycline en attendant les resultats pourrait ameliorer le pronostic des HLH.

MCR-1 in ESBL-producing Escherichia coli responsible for human infections in New Caledonia

Introduction La Nouvelle Caledonie est un territoire francais du Pacifique ou l’incidence de l’endocardite infectieuse (EI) et la prevalence du rhumatisme articulaire aigu (RAA) sont elevees. L’objectif de notre etude etait de decrire les EI a streptocoque sur ce territoire, de comparer leurs caracteristiques cliniques et evolutives en fonction du germe et du terrain. Materiels et methodes Les patients ayant une EI definie par les criteres de Dukes modifies hospitalises au centre hospitalier territorial de Noumea ont ete inclus de maniere prospective d’octobre 2010 a avril 2016. La classification des germes identifies dans les hemocultures a ete faite selon leurs caracteristiques genomiques. Les caracteristiques des patients et les complications des EI ont ete comparees en fonction du groupe (Pyogene versus autres streptocoques formant le groupe non Pyogene) et de la presence ou non de RAA valvulaire. Resultats Parmi 119 episodes d’EI, 37 (31 %) etaient dus a une infection a streptocoque. Parmi les 35 patients touches (2 cas d’EI recidivante), dix patients (29 %) avaient un antecedent de RAA valvulaire, dix (29 %) de valvulopathie degenerative, et onze (31 %) de remplacement valvulaire. Les episodes d’EI survenaient significativement plus precocement chez les patients aux antecedents de RAA qui etaient caracterises par un risque de recidive d’EI de 20 %. Des complications sont survenues dans 33 episodes d’EI (89 %) : neurologiques (16/37, 43 %), cardiaques (13/37, 35 %), osteo-articulaires (9/37, 26 %), choc septique (6/37, 16 %). Elles precedaient presque toujours le diagnostic d’EI (24 jours en moyenne). La mortalite etait de 11 % (4/37). Le risque d’AVC ischemique etait 5 fois moins eleve chez les patients avec RAA ( p = 0,06 non significatif). Les streptocoques du groupe non Pyogene etaient deux fois plus frequents que les streptocoques du groupe Pyogene. Streptococcus Pneumoniae , retrouve dans 7 episodes, etait associe a un risque de meningite et de choc septique significativement plus eleve que les autres streptocoques du groupe non Pyogene. Conclusion Les EI a streptocoque exposent a un risque eleve de complications, en particulier neurologiques (43 %). Les infections osteoarticulaires associees, souvent revelatrices, sont frequentes (26 %). La presentation et l’evolution des EI sont influencees par le germe et le terrain. Le RAA expose a un risque plus precoce d’EI mais pourrait etre associe a un moindre risque de complications neurologiques dans l’EI a streptocoque. Streptococcus Pneumoniae est responsable de formes severes d’EI.

Background Globally the diverse diseases associated with Streptococcus pyogenes infection are an important public health concern. Building on our recent discovery of a putative rheumatic heart disease susceptibility signal in the immunoglobulin heavy chain locus (IGH), we sought to identify variants in this poorly understood locus with shared and opposing effects on susceptibility to S pyogenes diseases focusing on rheumatic heart disease and invasive S pyogenes , which have mutually exclusive clinical phenotypes. Methods We conducted a comparative meta-analysis of our genome-wide association studies of susceptibility to rheumatic heart disease and invasive S pyogenes . Patients with rheumatic heart disease were recruited in Fiji, New Caledonia, and Samoa, and patients with invasive S pyogenes in the UK, Kenya, and New Caledonia. Controls were drawn from the same populations with additional controls for the rheumatic heart disease study from other Pacific Island nations. We searched for shared and opposing IGH loci using z-scores from the underlying analyses and used multinominal logistic regression to estimate effect sizes. Findings After quality control, there were 1028 cases and 2057 controls in the rheumatic heart disease study and 147 cases and 3003 controls in the invasive S pyogenes study with an overlap of 1669 common variants in the IGH locus. We identified a shared effect signal 3·4 kb upstream from the IGHV1-69 gene segment overlapping a putative transcription factor binding site and an opposing effect signal peaking at a missense variant in the second exon of the IGHV1-69 gene segment corresponding to the IGHV3-66*03 allele. After conditioning on the IGHV4-61*02 allele, which we have previously found associated with rheumatic heart disease, the lead shared effect single nucleotide polymorphism (SNP) (rs28627956) conferred increased risk of invasive S pyogenes but with negligible effect on risk of rheumatic heart disease (odds ratio 1·45 [95% CI 1·16–1·73] and 1·06 [0·87–1·24], respectively), whereas the lead opposing effect SNP (rs6423677) conferred reduced risk of invasive S pyogenes (0·75, 0·61–0·96) and increased risk of rheumatic heart disease (1·15, 0·98–1·38). Interpretation Germline IGH polymorphism is predicted to modify infectious and autoimmune disease susceptibility, although robust examples of such effects are scarce. Our results suggest that such polymorphism might have differential effects on susceptibility to S pyogenes disease, plausibly through coding and regulatory mechanisms. Our results provide new insight into the pathogenesis of these two neglected diseases as well as into the complex interplay between infectious and inflammatory disease. Funding British Heart Foundation, British Medical Association, European Society of Clinical Microbiology and Infectious Diseases, UK Medical Research Council, Wellcome Trust.

International audience; Case report without abstract

SUMMARYMelioidosis is an infectious disease caused byBurkholderia pseudomallei, a bacterium endemic in Southeast Asia and northern Australia. In New Caledonia, sporadic cases were first described in 2005; since then, more cases have been identified. To improve our understanding of melioidosis epidemiology in New Caledonia, we compared the local cases andB. pseudomalleiisolates with those from endemic areas. Nineteen melioidosis cases have been diagnosed in New Caledonia since 1999, mostly severe and with frequent bacteraemia, leading to three (16%) fatalities. All but one occurred in the North Province. Besides sporadic cases caused by non-clonal strains, we also identified a hotspot of transmission related to a clonal group ofB. pseudomalleithat is phylogenetically related to Australian strains.

Leptospira strains were isolated from freshwater sampled at four sites in Algeria and characterized by whole-genome sequencing and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The cells were spiral-shaped and motile. Phylogenetic and MALDI-TOF MS analyses showed that the strains can be clearly distinguished from the other described species in the genus Leptospir a, therefore representing two novel species of the pathogen subclade P1 and two novel species of the saprophyte subclade S1. The names Leptospira ainlahdjerensis sp. nov. (type strain 201903070T=KIT0297T=CIP111912T), Leptospira ainazelensis sp. nov. (201903071T=KIT0298T=CIP111913T), Leptospira abararensis sp. nov. (201903074T=KIT0299T=CIP111914T) and Leptospira chreensis (201903075T=KIT0300T=CIP111915T) are proposed.

Introduction: The increasing number of cases of isolation of Corynebacterium diphtheriae in New Caledonia, the potential severity of this infection and the consequences in terms of public health actions have prompted us to focus on this bacterial species and its local epidemiology. Material and method: A retrospective clinical study was conducted by consulting patient records for each of the 84 cases included. Among these cases, 58 were retained, for which the antibiograms were retested, the tox gene sought, the biovar determined, the strains sequenced and a phylogenetic tree carried out based on the core genome of our cohort. Results: We note a concentration of cases particularly around Nouméa and Lifou. 84% of samples were taken at skin level. Overall the strains present in the territory are sensitive to the majority of commonly used antibiotics. However, 27.9% of tetracycline-resistant strains were found. 63.7% of our strains belong to only two sublineages, few found elsewhere in the world. The vast majority of strains do not express diphtheria toxin, except for two episodes, one case and five cases, all imported from Vanuatu. Discussion: The evolution of the repositories used for the realization of antibiograms tends to make strains more often resistant without biological reality when the same technique is applied to all strains. Asymptomatic portages and incidental discoveries suggest that there is a significant number of tox - strains in New Caledonia, a potential reservoir in case of introduction of tox+ strains via Vanuatu for example. This should motivate particular attention to population immunization coverage.; Introduction : Le nombre croissant d’isolement de Corynebacterium diphtheriae relevé en Nouvelle-Calédonie, la potentielle gravité de cette infection et la répercussion en termes d’actions de santé publique à mettre en place nous ont incités à nous intéresser plus particulièrement à cette espèce bactérienne et à son épidémiologie locale. Matériel et méthode : Une étude clinique rétrospective a été réalisée par consultation des dossiers patients pour chacun des 84 épisodes inclus. Parmi ces cas, 58 ont été conservés, pour lesquelles les antibiogrammes ont été retestés, le gène tox recherché, le biovar déterminé, les souches séquencées et un arbre phylogénétique a été réalisé en se basant sur le core génome de notre cohorte. Résultats : Nous notons une concentration des cas en particulier autour de Nouméa et Lifou. 84 % des prélèvements ont été réalisés au niveau cutané. Les souches présentes sur le territoire sont globalement sensibles à la majorité des antibiotiques couramment utilisés. On note cependant 27,9 % de souches résistantes à la tétracycline. 63,7 % de nos souches appartiennent à seulement deux sublineages, peu retrouvés ailleurs dans le monde. Les souches dans leur grande majorité n’expriment pas la toxine diphtérique, excepté deux épisodes, de 1 cas et 5 cas, tous importés du Vanuatu. Discussion : L’évolution des référentiels utilisés pour la réalisation des antibiogrammes tend à rendre les souches plus souvent résistantes sans réalité biologique lorsque l’on applique la même technique à toutes les souches. Des portages asymptomatiques et découvertes fortuites font penser qu’il y a un nombre important de souches tox- en Nouvelle-Calédonie, réservoir potentiel en cas d’introduction de souches tox+ via le Vanuatu par exemple. Cela doit susciter une attention particulière en ce qui concerne la couverture vaccinale de la population.

The zoonotic bacterium Leptospira interrogans is the aetiological agent of leptospirosis, a re-emerging infectious disease that is a growing public health concern. Most human cases of leptospirosis result from environmental infection. Biofilm formation and its contribution to the persistence of virulent leptospires in the environment or in the host have scarcely been addressed. Here, we examined spatial and time-domain changes in biofilm production by L. interrogans. Our observations showed that biofilm formation in L. interrogans is a highly dynamic process and leads to a polarized architecture. We notably found that the biofilm matrix is composed of extracellular DNA, which enhances the biofilm’s cohesiveness. By studying L. interrogans mutants with defective diguanylate cyclase and phosphodiesterase genes, we show that biofilm production is regulated by intracellular levels of bis-(3′–5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) and underpins the bacterium’s ability to withstand a wide variety of simulated environmental stresses. Our present results show how the c-di-GMP pathway regulates biofilm formation by L. interrogans, provide insights into the environmental persistence of L. interrogans and, more generally, highlight leptospirosis as an environment-borne threat to human health.

International audience; Leptospirosis is an important environmental disease and a major threat to human health causing at least 1 million clinical infections annually. There has recently been a growing interest in understanding the environmental lifestyle of Leptospira. However, Leptospira isolation from complex environmental samples is difficult and time-consuming and few tools are available to identify Leptospira isolates at the species level. Here, we propose a polyphasic isolation and identification scheme, which might prove useful to recover and identify environmental isolates and select those to be submitted to whole-genome sequencing. Using this approach, we recently described 12 novel Leptospira species for which we propose names. We also show that MALDI-ToF MS allows rapid and reliable identification and provide an extensive database of Leptospira MALDI-ToF mass spectra, which will be valuable to researchers in the leptospirosis community for species identification. Lastly, we also re-evaluate some of the current techniques for the molecular diagnosis of leptospirosis taking into account the extensive and recently revealed biodiversity of Leptospira in the environment. In conclusion, we describe our method for isolating Leptospira from the environment, confirm the usefulness of mass spectrometry for species identification and propose names for 12 novel species. This also offers the opportunity to refine current molecular diagnostic tools.