Genomic Epidemiology of Corynebacterium diphtheriae in New Caledonia.

An increasing number of isolations of Corynebacterium diphtheriae has been observed in recent years in the archipelago of New Caledonia. We aimed to analyze the clinical and microbiological features of samples with C. diphtheriae. All C. diphtheriae isolates 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, tox gene 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. Fifty-eight 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, and C. diphtheriae was associated with Staphylococcus aureus and/or Streptococcus pyogenes in 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 the tetO gene. There were 13 cgMLST sublineages, most of which were also observed in the neighboring country Australia. Cutaneous infections may harbor nontoxigenic C. diphtheriae isolates, which circulate largely silently in nonspecific 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. IMPORTANCE The analysis of C. diphtheriae from the tropical archipelago of New Caledonia revealed a high genetic diversity with sublineages that may be linked to Polynesia, Australia, or metropolitan France. Genomic typing allowed confirming or excluding suspected transmission events among cases and contacts. A highly prevalent tetracycline-resistant sublineage harboring the tetO gene was uncovered. Toxigenic isolates were observed from patients returning from Vanuatu, showing the importance of improving vaccination coverage in settings where it is insufficient. This study also illustrates the importance for diphtheria surveillance of the inclusion of isolates from cutaneous sources in addition to respiratory cases, in order to provide a more complete epidemiological picture of the diversity and transmission of C. diphtheriae.

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.

Prevalence of Silent Atherosclerosis and Other Comorbidities in an Outpatient Cohort of Adults Living with HIV: Associations with HIV Parameters and Biomarkers.

People living with HIV (PLWH) are at risk of noninfectious comorbidities. It is important to individualize those at higher risk. In a single-center cohort of PLWH, we performed a cross-sectional analysis of comorbidities, diagnosed according to standard procedures. The primary endpoint was the prevalence of subclinical carotid/coronary atherosclerosis. Secondary endpoints were its association with selected inflammatory/immune activation biomarkers and with other comorbidities. Associations were examined by using Chi-square or Fisher's exact test for categorical variables and Student or Wilcoxon tests for quantitative variables, and a stepwise multivariate logistical model was performed for further exploration. Among 790 participants [median age: 49.8 years (interquartile range, IQR: 44.5-55.6), 77.1% males, median CD4: 536/mm3 (IQR: 390-754), 83.6% with undetectable viral load], asymptomatic atherosclerosis was found in 26% and was associated in multivariate analysis with older age, longer known duration of infection, higher sCD14, and lower adiponectin levels. Hypertension was found in 33.5% of participants, diabetes in 19.4%, renal impairment in 14.6%, elevated low-density lipoprotein-cholesterol in 13.3%, elevated triglyceride/high-density lipoprotein (HDL)-cholesterol ratio in 6.6%, and osteoporosis in 7.9%. The presence of two or more comorbidities was found in 42.1% of participants and was associated in multivariate analysis with older age and longer exposure to antiretrovirals. Comorbidities were diversely associated with biomarkers: osteoporosis with higher IL-6, renal impairment with higher sCD14, hypertension with higher D-dimer, diabetes and elevated triglyceride/HDL-cholesterol ratio both with lower adiponectin and lower 25-hydroxyvitamin D. Asymptomatic atherosclerosis and multimorbidity were frequent in a cohort of middle-aged, well-controlled, PLWH and were associated with traditional and HIV-specific factors. Associations between morbidities and inflammatory/immune activation biomarkers were diverse.

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.

Prognostic factors of calcaneal osteomyelitis.

BACKGROUND: Calcaneal osteomyelitis is difficult to manage and requires a multidisciplinary approach. The aim of this study was to describe the characteristics and outcomes of calcaneal osteomyelitis, and to determine prognostic factors. METHODS: This was an observational and retrospective study including all patients presenting with calcaneal osteomyelitis referred to a tertiary referral centre between January 2005 and December 2010. RESULTS: Forty-two patients (mean age 50.7 y, range 22-89 y) were included. Fifteen were female. The mean duration of follow-up was 20 months (range 12-48 months). Twenty-six (62%) were post-traumatic osteomyelitis and 16 (38%) were secondary to neurological damage (sensitivity or motor impairment). All patients underwent surgical management with bone curettage and appropriate antibiotic therapy. Staphylococcus aureus was the most commonly isolated bacterium and was found in 29 patients. Polymicrobial samples were observed in 29 patients. Pseudomonas aeruginosa was associated with calcaneal osteomyelitis secondary to neurological damage (n = 7; 44% p = 0.045). Twenty-eight patients (66.7%) healed without the need to resort to amputation. The mean time to healing was 29 weeks with a range of 4-144 weeks. Relapse of bone infection occurred in 17 patients (40.5%). Seven patients (16.7%) required amputations. Favourable prognostic factors for healing without amputation were an American Society of Anesthesiologists (ASA) score < 2 (p < 10(-4)), post-traumatic calcaneal osteomyelitis (p = 0.001), age < 65 y (p = 0.02), absence of neuropathy (p = 0.005), and absence of diabetes mellitus (p = 0.02). CONCLUSIONS: Calcaneal osteomyelitis is characterized by frequent relapse with delayed wound healing. Clinicians should take into account the impact of older age, as well as co-morbidities such as diabetes mellitus or the presence of neuropathy, during the routine management of patients with this difficult-to-treat bone infection.