Background Biological control programs involving Wolbachia-infected Aedes aegypti are currently deployed in different epidemiological settings. New Caledonia (NC) is an ideal location for the implementation and evaluation of such a strategy as the only proven vector for dengue virus (DENV) is Ae. aegypti and dengue outbreaks frequency and severity are increasing. We report the generation of a NC Wolbachia-infected Ae. aegypti strain and the results of experiments to assess the vector competence and fitness of this strain for future implementation as a disease control strategy in Noumea, NC. Methods/principal findings The NC Wolbachia strain (NC-wMel) was obtained by backcrossing Australian AUS-wMel females with New Caledonian Wild-Type (NC-WT) males. Blocking of DENV, chikungunya (CHIKV), and Zika (ZIKV) viruses were evaluated via mosquito oral feeding experiments and intrathoracic DENV challenge. Significant reduction in infection rates were observed for NC-wMel Ae. aegypti compared to WT Ae. aegypti. No transmission was observed for NC-wMel Ae. aegypti. Maternal transmission, cytoplasmic incompatibility, fertility, fecundity, wing length, and insecticide resistance were also assessed in laboratory experiments. Ae. aegypti NC-wMel showed complete cytoplasmic incompatibility and a strong maternal transmission. Ae. aegypti NC-wMel fitness seemed to be reduced compared to NC-WT Ae. aegypti and AUS-wMel Ae. aegypti regarding fertility and fecundity. However further experiments are required to assess it accurately. Conclusions/significance Our results demonstrated that the NC-wMel Ae. aegypti strain is a strong inhibitor of DENV, CHIKV, and ZIKV infection and prevents transmission of infectious viral particles in mosquito saliva. Furthermore, our NC-wMel Ae. aegypti strain induces reproductive cytoplasmic incompatibility with minimal apparent fitness costs and high maternal transmission, supporting field-releases in Noumea, NC.

BackgroundHuman T-Lymphotropic Virus type 1 (HTLV-1) is endemic among people of Melanesian descent in Papua New Guinea, Solomon Islands and Vanuatu, and in Indigenous populations from Central Australia. Molecular studies revealed that these Australo-Melanesian strains constitute the highly divergent HTLV-1c subtype. New Caledonia is a French overseas territory located in the Southwest Pacific Ocean. HTLV-1 situation is poorly documented in New Caledonia and the molecular epidemiology of HTLV-1 infection remains unknown.ObjectivesStudying 500 older adults Melanesian natives from New Caledonia, we aim to evaluate the HTLV-1 seroprevalence and to molecularly characterize HTLV-1 proviral strains.Study designPlasma from 262 men and 238 females (age range: 60–96 years old, mean age: 70.5) were screened for anti-HTLV-1 antibodies by particle agglutination (PA) and indirect immunofluorescence assay (IFA). Serological confirmation was obtained using Western blot assay. DNAs were extracted from peripheral blood buffy coat of HTLV-1 seropositive individuals, and subjected to four series of PCR (LTR-gag; pro-pol; pol-env and tax-LTR). Primers were designed from highly common conserved regions of the major HTLV-1 subtypes to characterize the entire HTLV-1 proviral genome.ResultsAmong 500 samples, 3 were PA and IFA positive. The overall seroprevalence was 0.6%. The DNA sample from 1 New Caledonian woman (NCP201) was found positive by PCR and the complete HTLV-1 proviral genome (9,033-bp) was obtained. The full-length HTLV-1 genomic sequence from a native woman from Vanuatu (EM5), obtained in the frame of our previous studies, was also characterized. Both sequences belonged to the HTLV-1c Australo-Melanesian subtype. The NCP201 strain exhibited 0.3% nucleotide divergence with the EM5 strain from Vanuatu. Furthermore, divergence reached 1.1% to 2.9% with the Solomon and Australian sequences respectively. Phylogenetic analyses on a 522-bp-long fragment of the gp21-env gene showed the existence of two major clades. The first is composed of strains from Papua New Guinea; the second includes strains from all neighboring archipelagos (Solomon, Vanuatu, New Caledonia), and Australia. Interestingly, this second clade itself is divided into two sub-clades: strains from Australia on one hand, and strains from Solomon Islands, Vanuatu and New Caledonia on the other hand.ConclusionsThe HTLV-1 seroprevalence (0.6%) in the studied adult population from New Caledonia appears to be low. This seroprevalence is quite similar to the situation observed in Vanuatu and Solomon Islands. However it is very different to the one encountered in Central Australia. Taken together, these results demonstrated that Australo-Melanesia is endemic for HTLV-1 infection with a high diversity of HTLV-1c strains and a clear geographic clustering according to the island of origin of HTLV-1 infected persons.

La situation sanitaire de la Nouvelle-Calédonie présente les données de l'année 2015 ainsi que les évolutions des années précédentes. L'année 2015 a été marquée notamment par la circulation des trois arboviroses : dengue, chikungunya et zika. Le renforcement des mesures de contrôle sanitaire aux frontières et les actions de lutte anti-vectorielle menées par l'ensemble des partenaires ont permis d'éviter la survenue d'une épidémie. Ce bilan 2015 restitue par ailleurs l'ensemble des données recueillies par le service de santé publique de la direction des affaires sanitaires et sociales de la Nouvelle-Calédonie. Il a pu être élaboré grâce à la collaboration de tous les partenaires, médecins, institutions qui oeuvrent directement ou indirectement pour améliorer la santé de la population calédonienne. Qu'ils en soient remerciés pour leur contribution à cette mission et leur participation à l'élaboration de ce document, tout comme des remerciements particuliers sont également adressés à ceux qui ont fourni des synthèses ou qui ont rédigé des chapitres. Le soutien constant des directions des actions sanitaires et sociales des trois Provinces mérite d'être souligné. Enfin, il faut remercier l'équipe du service de santé publique pour la quantité et la qualité du travail fourni depuis la collecte, l'analyse et la rédaction de ce rapport, qui a pu être mené à bien en dépit d'une équipe réduite pendant l'année 2016. Certains recueils sont exhaustifs. D'autres données proviennent d'études spécifiques, des réseaux sentinelles, des bilans d'activité des établissements et structures de santé, et sont représentatifs de la situation réelle. Cependant, pour d'autres recueils, tributaires des déclarations des professionnels de santé et d'autres partenaires, les données sont incomplètes du fait de sous-déclarations. De ce fait, les chiffres ne représentent pas l'incidence exacte de certaines pathologies. Elles restent cependant des indicateurs essentiels pour le suivi des tendances. Cette situation nous impose d'améliorer encore la qualité du recueil ainsi que la participation des professionnels de santé, notamment le secteur libéral de Nouméa, pour parfaire cet outil indispensable à l'élaboration de la politique de santé. La lecture de ce document doit tenir compte des commentaires et, dans certains cas, ne pas être interprétés de manière hâtive. Plus encore, lorsque des réserves méthodologiques sont énoncées. Ce document représente un constat à un moment donné. C'est un outil, remis à jour chaque année, indispensable pour guider la réflexion, le choix et les interventions de tous les acteurs de la santé publique. Il est encore incomplet, les résultats et leur présentation demeurent perfectibles. Toutes vos remarques et vos suggestions seront les bienvenues et permettront l'enrichissement de nos connaissances mutuelles. Le site Internet de la DASS-NC (www.dass.gouv.nc) vous permet de télécharger la situation sanitaire de la Nouvelle-Calédonie sur l'année en cours et les années précédentes. Nous ne pouvons que vous recommander de con...

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BackgroundElevated lactate is known to favor urine urate reabsorption by the URAT1 urate/anion exchanger. Autosomal recessive gout caused by pathogenic variant in the LDHD gene encoding for D-lactate deshydrogenase has been recently identified in a large consanguineous Bedouin-Israeli kindred (1).ObjectivesWe report here on two families in whom early-onset gout was linked to other variants leading to deficient D-LDH enzymes.MethodsStudies of the two families were approved by appropriate Ethics committees. Whole exome sequencing (WES) was used to identify the genetic cause of familial gout. Dosages of D-lactate were performed on immediately frozen serum and urine samples by ELISA, using a D-lactate colorimetric assay kit (Abcam ab83429).ResultsFamily 1 was Melanesian, living in the Lifou island of New Caledonia. The two index patients were two sisters who developed gout at the age of 13 and 16 years respectively. When seen at the ages of 25 and 27 years, they both had severe gout with frequent polyarticular flares, and multiple tophi and destructive arthropathies in the earliest age of onset one. WES, performed on the 2 affected sisters, their non-consanguine parents, and an unaffected brother, showed that the 2 affected sisters carried homozygous rare variant in DLDH gene (NM_153486.3: c.206 C>T; rs1035398551). This variant was at heterozygote level in both parents and absent in the unaffected brother. It was considered as probably damaging according to in silico prediction software. No association with any other gene was found.The c.206C>T variant in LDHD was searched by Sanger sequencing method in 13 other extended family members. One 23 year-old brother of the two diseased sisters with atypical MTP flares, high uricemia and double contours at US examination of his MTPs, carried the c.206 C>T variant at the homozygous level. Three other heterozygous patients were found; two of whom were male with late-onset gout, the third one being a non-menopausal female with no gout. No variant carrier was found in the other 9 genotyped family members. The 3 homozygous patients for the c.206 C>T variant had very high hyperuricemia (range 738-834 was searched by Sanger sequencing method in 13 other extended family members. One 23 year-old brother of the two diseased sisters with atypical MTP flares, high uricemia and double contours at US examination of had very low or no D-lactate in plasma and urine. L-lactate blood and urine levels were normal in all subjects.Family 2 was Vietnamese, living in a remote area of central Vietnam. The two affected children suffered from an extremely severe, destructive gout, which started at the age of 21 years in a daughter and at the age of 9 in her youngest brother, who had developed for the last 3 years, dysarthria, night shakes, memory loss, urine incontinence and an inability to read and count and died at the age of 34, a few months after being seen by us. WES was performed in the two probands, their father and mother (who denied consanguinity), and an unaffected brother. An undescribed variant in LDHD (NM_153486.3: c.1363dupG) was identified in homozygous level in the 2 juvenile gout patients and at the heterozygous level in their 2 parents and unaffected brother. This variant led to a frameshift followed by a stop codon p.(AlaGly432fsTer58). In addition, the two juvenile gout patients were homozygous for an undescribed frameshift (NR_046115.1: c.1064dup) variant of the RHBG gene encoding for a Rhesus Blood Group family ammonium transporter. The two parents carried the heterozygous variant which was not identified in the non-gout brother.ConclusionWe report on 2 families in whom autosomal recessive juvenile gout was due to rare or undescribed, damaging LDHD gene variants. In addition, we observed in the Vietnamese family, an additional non-described frameshift homozygous variant in RHBG, the pathophysiological role of which deserves to be investigated.References[1]Drabkin M et al. Hyperuricemia and gout caused by missense mutation in D-lactate dehydrogenase. J Clin Invest. 2019;129:5163-5168Disclosure of InterestsThomas Bardin Consultant of: leo Pharma, Yves-Marie Ducrot: None declared, Quang Nguyen: None declared, Emmanuel Letavernier: None declared, Hang-Korng Ea: None declared, Frederic Touzain: None declared, Duc Minh Do: None declared, Julien Corot: None declared, Yan Barguil: None declared, Antoine Biron: None declared, Pascal Richette: None declared, Corinne Collet: None declared