Clinical Evaluation of the Modified Faine Criteria in Patients Admitted with Suspected Leptospirosis to the Territorial Hospital, New Caledonia, 2018 to 2019.

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.

Development of a bedside score to predict dengue severity.

BACKGROUND: In 2017, New Caledonia experienced an outbreak of severe dengue causing high hospital burden (4379 cases, 416 hospital admissions, 15 deaths). We decided to build a local operational model predictive of dengue severity, which was needed to ease the healthcare circuit. METHODS: We retrospectively analyzed clinical and biological parameters associated with severe dengue in the cohort of patients hospitalized at the Territorial Hospital between January and July 2017 with confirmed dengue, in order to elaborate a comprehensive patient's score. Patients were compared in univariate and multivariate analyses. Predictive models for severity were built using a descending step-wise method. RESULTS: Out of 383 included patients, 130 (34%) developed severe dengue and 13 (3.4%) died. Major risk factors identified in univariate analysis were: age, comorbidities, presence of at least one alert sign, platelets count < 30 × 109/L, prothrombin time < 60%, AST and/or ALT > 10 N, and previous dengue infection. Severity was not influenced by the infecting dengue serotype nor by previous Zika infection. Two models to predict dengue severity were built according to sex. Best models for females and males had respectively a median Area Under the Curve = 0.80 and 0.88, a sensitivity = 84.5 and 84.5%, a specificity = 78.6 and 95.5%, a positive predictive value = 63.3 and 92.9%, a negative predictive value = 92.8 and 91.3%. Models were secondarily validated on 130 patients hospitalized for dengue in 2018. CONCLUSION: We built robust and efficient models to calculate a bedside score able to predict dengue severity in our setting. We propose the spreadsheet for dengue severity score calculations to health practitioners facing dengue outbreaks of enhanced severity in order to improve patients' medical management and hospitalization flow.

Flying Fox Hemolytic Fever, Description of a New Zoonosis Caused by Candidatus Mycoplasma haemohominis.

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.

Corynebacterium striatum thrombophlebitis: a nosocomial multidrug-resistant disease?

INTRODUCTION: Corynebacterium striatum is a non-Diphteriae commensal bacterium with a wide range of pathogenicity. The identification of multidrug-resistant (MDR) C. striatum is concerning because drug susceptibility testing is not usually performed in microbiology laboratories. There is no consensus yet on the treatment of septic thrombophlebitis in this situation. CASE REPORT: We report here the first case of a quinquagenarian patient with a history of AIDS and fungic endocarditis, who was diagnosed with a nosocomial thrombophlebitis in the right jugular vein caused by C. striatum . Bitherapy with daptomycin for 12 days and linezolid for 23 days was combined with a therapeutic anticoagulant. The follow-up included weekly cervical ultrasound controls. The efficiency of the treatment and the stability of the lesions allowed us to alleviate the medication with a prophylactic dose of anticoagulant. The patient was discharged from hospital and showed no signs of recurrence after 12 months. CONCLUSION: The lack of consensus relative to the management of septic thrombophlebitis precludes the validation of a specific treatment for the condition. Our results suggest that a combination that includes removal of the medical device is needed. A total of 6 weeks of antibiotherapy should be applied, starting with 2 weeks of vancomycin or a combination of antibiotitherapy with daptomycin in order to reduce the bacterial load and avoid resistance. Six weeks of anticoagulation therapy is effective.

Age-specific epidemiology of human leptospirosis in New Caledonia, 2006-2016.

With over one million cases worldwide annually and a high fatality in symptomatic forms, human leptospirosis is a growing public health concern for the most vulnerable populations, especially in the context of global warming and unplanned urbanization. Although the Asia-Pacific region is particularly affected, accurate epidemiological data are often lacking. We conducted an eleven-year retrospective laboratory-based epidemiological survey of human leptospirosis in New Caledonia. From 2006 to 2016, 904 cases were laboratory-confirmed, including 29 fatalities, corresponding to an average annual incidence of 30.6/100,000 and a case fatality rate of 3.2%. Over the period, there was a major shift from indirect serological diagnosis by MAT to direct diagnosis by real-time PCR, a more specific and sensitive test when performed early in the course of the disease. The systematic implementation of genotyping informed on the variety of the infective strains involved, with a predominance of serogroups Icterohaemorrhagiae and Pyrogenes. The epidemiological pattern showed a marked seasonality with an annual peak in March-April. Interestingly, the seasonal peak in children of school age was significantly earlier and corresponded to school holidays, suggesting that attending school from February on could protect children from environment-borne leptospirosis.

Evolution of viral quasispecies during SARS-CoV-2 infection.

OBJECTIVES: Studies are needed to better understand the genomic evolution of the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to describe genomic diversity of SARS-CoV-2 by next-generation sequencing (NGS) in a patient with longitudinal follow-up for SARS-CoV-2 infection. METHODS: Sequential samples collected between January 29th and February 4th, 2020, from a patient infected by SARS-CoV-2 were used to perform amplification of two genome fragments-including genes encoding spike, envelope, membrane and nucleocapsid proteins-and NGS was carried out with Illumina® technology. Phylogenetic analysis was performed with PhyML and viral variant identification with VarScan. RESULTS: Majority consensus sequences were identical in most of the samples (5/7) and differed in one synonymous mutation from the Wuhan reference sequence. We identified 233 variants; each sample harboured in median 38 different minority variants, and only four were shared by different samples. The frequency of mutation was similar between genes and correlated with the length of the gene (r = 0.93, p = 0.0002). Most of mutations were substitution variations (n = 217, 93.1%) and about 50% had moderate or high impact on gene expression. Viral variants also differed between lower and upper respiratory tract samples collected on the same day, suggesting independent sites of replication of SARS-CoV-2. CONCLUSIONS: We report for the first time minority viral populations representing up to 1% during the course of SARS-CoV-2 infection. Quasispecies were different from one day to the next, as well as between anatomical sites, suggesting that in vivo this new coronavirus appears as a complex and dynamic distributions of variants.

Counting Oceanians of Non-European, Non-Asian Descent (ONENA) in the South Pacific to Make Them Count in Global Health.

Several diseases and vulnerabilities associated with genetic or microbial factors are more frequent among populations of Oceanian, Non-European, Non-Asian descent (ONENA). ONENA are specific and have long been isolated geographically. To our knowledge, there are no published official, quantitative, aggregated data on the populations impacted by these excess vulnerabilities in Oceania. We searched official census reports for updated estimates of the total population for each of the Pacific Island Countries and Territories (including Australia) and the US State of Hawaii, privileging local official statistical or censual sources. We multiplied the most recent total population estimate by the cumulative percentage of the ONENA population as determined in official reports. Including Australia and the US State of Hawaii, Oceania counts 27 countries and territories, populated in 2016 by approximately 41 M inhabitants (17 M not counting Australia) among which approximately 12.5 M (11.6 M not counting Australia) consider themselves of entire or partial ONENA ancestry. Specific genetic and microbiome traits of ONENA may be unique and need further investigation to adjust risk estimates, risk prevention, diagnostic and therapeutic strategies, to the benefit of populations in the Pacific and beyond.

Dengue in New Caledonia: Knowledge and Gaps.

Arboviruses are viruses transmitted to humans by the bite of infected mosquito vectors. Over the last decade, arbovirus circulation has increasingly been detected in New Caledonia (NC), a French island territory located in the subtropical Pacific region. Reliable epidemiological, entomological, virological and climate data have been collected in NC over the last decade. Here, we describe these data and how they inform arboviruses' epidemiological profile. We pinpoint areas which remain to be investigated to fully understand the peculiar epidemiological profile of arbovirus circulation in NC. Further, we discuss the advantages of conducting studies on arboviruses dynamics in NC. Overall, we show that conclusions drawn from observations conducted in NC may inform epidemiological risk assessments elsewhere and may be vital to guide surveillance and response, both in New Caledonia and beyond.