A multicenter, randomized, open-label, controlled study comparing the efficacy, safety and cost-effectiveness of a sequential therapy with RV4104A ointment, ciclopiroxolamine cream and ciclopirox film-forming solution with amorolfine nail lacquer alone in dermatophytic onychomycosis.

BACKGROUND: The efficacy of topical antifungals is controversial. OBJECTIVE: To compare the efficacy and safety of a sequential(SEQ) treatment with chemical nail avulsion and topical antifungals to amorolfine nail lacquer in dermatophytic onychomycosis. METHODS: This was a randomized,parallel-group, controlled study comparing a 36-week SEQ treatment with chemical nail avulsion with RV4104A ointment(class I medical device containing 40% urea) followed by ciclopirox cream for 8 weeks and ciclopirox nail lacquer for 25 weeks (SEQ group) to amorolfine nail lacquer for 36 weeks (AMO group). Patients had to have a big toenail onychomycosis,sparing the matrix. The primary efficacy criterion was complete cure at week 48. A cost-effectiveness analysis was performed. RESULTS: A total of 142 patients were randomized. The complete cure rate at week 48 was significantly higher in the SEQ group than in the AMO group (36.6 vs. 12.7%, p = 0.001). Clinical cure at week 48 was observed in 53.5% of patients in the SEQ group versus 17% in the AMO group (p < 0.01). The cost of cure per patient was 50% lower with SEQ treatment (EUR 33) compared with amorolfine(EUR 76). CONCLUSION: A treatment of onychomycosis comprising chemical avulsion of the pathological nail, ciclopirox cream and nail lacquer is significantly more effective than amorolfine nail lacquer.

Invasive aspergillosis: an important risk factor on the short- and long-term survival of acute myeloid leukemia (AML) patients.

Invasive aspergillosis (IA) during induction chemotherapy of acute myeloid leukemia (AML) could worsen the prognosis. Our objective was to study how the development of IA during AML interferes with the therapeutic strategy and to evaluate its impact on the short- and long-term survival. Newly diagnosed AML patients between the years 2004 and 2007 were retrospectively analyzed. The outcome was death of the patient. A Cox proportional hazards model with the diagnosis of IA and post-induction response evaluation as the main exposure was fitted. Overall, 262 patients were analyzed and 58 IA were observed. The 2-year survival of patients having had remission of AML was 54% and, for patients with failure of chemotherapy, it was 5% (p < 0.001). The 2-year survival of patients having had IA was 14%, and without IA, it was 32% (p = 0.01). Multivariate analysis showed that IA was associated with a higher risk of death in case of remission compared to no IA (hazard ratio [HR] = 1.66 [1.05-2.65], p = 0.031) and also in case of failure (HR = 6.43, p < 0.001). IA was associated with an increased risk of death for patients if they were either in remission or in failure after induction chemotherapy.

Dual shape recovery of red blood cells flowing out of a microfluidic constriction.

Micropipette aspiration, optical tweezers, rheometry, or ecktacytometry have been used to study the shape recovery of healthy human Red Blood Cells (RBCs) and measure associated relaxation times of the order of 100-300 ms. These measurements are in good agreement with the Kelvin-Voigt model, which describes the cell as a visco-elastic material, predicting that its relaxation time only depends on cell intrinsic properties. However, such mechanical solicitation techniques are far from being relevant regarding RBC solicitation in vivo. In this paper, we report for the first time the existence of two different behaviors of the RBC shape recovery while flowing out of a microfluidic constricted channel. The calculation of the viscous stress corresponding to the frontier between the two recovery modes confirms that the RBC resistance to shear µ is the elastic property dominating the transition between the two recovery behaviors. We also quantified associated recovery times τ r and report values as low as 4 ms-which is almost two decades smaller than the typical RBC relaxation time-at high viscosity and flow velocity of the carrier fluid. Although we cannot talk about relaxation time because the cell is never at rest, we believe that the measured shape recovery time arises from the coupling of the cell intrinsic deformability and the hydrodynamic stress. Depending on the flow conditions, the cell mechanics becomes dominant and drives the shape recovery process, allowing the measurement of recovery times of the same order of magnitude than relaxation times previously published. Finally, we demonstrated that the measurement of the shape recovery time can be used to distinguish Plasmodium falciparum (causing malaria) infected RBCs from healthy RBCs.

The mariner transposable element in natural populations of Drosophila simulans.

In cosmopolitan species, geographical variations in copy number and/or level of transposition activity have been observed for several transposable elements (TEs). Environment, history and population structure can contribute to such variation in ways that are difficult to tease apart. For the mariner element, previous studies of the geographic variation of its somatic activity in natural populations of Drosophila simulans have shown contradictory results (latitudinal clines of divergent orientations or no apparent structure). To try and resolve these inconsistencies, we gathered all available data on the mariner somatic activity of worldwide natural populations. This includes previously published results by different groups and also new data. The correlations between the level of activity and several geoclimatic factors were tested. Although no general effect of temperature was found, a relationship with the invasion history was detected. It was also shown that recent invasive populations have a higher level of activity than the putative ancestral ones. Our results strongly suggest that variability of the mariner somatic activity among natural populations of D. simulans is mainly due to populational and historical factors probably related to the recent world colonization of this species. Indeed, this activity is correlated to the main route out of Africa (the Nile route) and the recent colonization of continents such as Australia and South America.

[New use of primaquine for malaria]. / Le nouvel âge de la primaquine contre le paludisme.

Primaquine is the only available drug to treat Plasmodium vivax liver stages (hypnozoites). It has been used for more than five decades and is now included in an increasing number of clinical guidelines. The major concern is induced hemolysis when administered to glucose-6-phosphate-dehydrogenase deficient patients. Primaquine could be used for causal prophylaxis during and after exposure or for presumptive antirelapse therapy (PART) in case of high exposure to P. vivax. A radical cure is used to avoid relapse for patients with a confirmed bloodstream infection with P. vivax or P. ovale. In France, primaquine is not approved for prevention and treatment and its use requires a specific temporary authorization.

[Early onset neonatal infections in the South of the Reunion Island: Incidence and use of 2002 ANAES risk criteria]. / Infection bactérienne néonatale précoce dans le sud de la Réunion: incidence et application des critères de risque Anaes 2002.

OBJECTIVES: The aim of this study was to describe the incidence of early onset neonatal infections (EONI) in the southern part of the Reunion Island, and to study the application of ANAES criteria. PATIENTS AND METHODS: A cross-sectional study was made of data collected for all live births having occurred between 1st January 2001 and 31st December 2004. RESULTS: Four hundred and thirty-seven in 16,071 neonates (out of 21,231 live births) presented with a certain or probable EONI, accounting for a regional rate of 20 per thousand (CI95 % 18-23 per thousand). Among 437 EONIs, group B streptococcus (GBS) was reported in 70.5% of the cases (n=308), Gram negative bacteria in 19.9% (n=87), of which nearly two thirds of Escherichia coli (n=56). Applying ANAES criteria led to identify 380 EONIs among 437 proven infections (sensitivity: 87%, specificity: 26%). A logistic regression analysis identified eight EONI predictors for the 7015 neonates for whom the mother GBS screening was documented: GBS positive vaginal culture (OR 4.2; CI95% 3.3-5.4), unexplained preterm birth less than 35 weeks (OR 5.7; CI95% 3.7-8.7), prolonged rupture of membranes greater than or equal to 18 hours (OR 2.1; CI95% 1.4-3.0), maternal fever greater than or equal to 37.8 degrees C (OR 3.2; CI95% 2.3-4.5), fetal tachycardia greater than or equal to 160 ppm (OR 2.7; CI95% 1.8-4.0), and thin (OR 1.6; CI95% 1.2-2.1) or thick meconium-stained amniotic fluid (OR 3.0; CI95% 2.1-4.5) or fetid fluid (OR 14.8; CI95% 4.2-51.8). CONCLUSION: The incidence of EONIS far exceeded that observed in metropolitan France, and the ANAES criteria lack sensitivity and specificity.

[Fungal keratitis: A 5-year monocentric retrospective study on Reunion Island]. / Kératites fongiques : étude rétrospective monocentrique sur 5ans à l'île de la Réunion.

OBJECTIVES: Fungal keratitis is rare in France, but could be a severe sight-threatening condition. Here, we aimed to describe the epidemiology of fungal keratitis in Réunion Island. METHODS: In a retrospective study, we analyzed 13 culture-proven keratitis episodes, occurred between January 2013 and July 2017 in the ophthalmology ward of a University Hospital, Saint-Pierre. Twelve isolates were genotyped and antifungal susceptibility testing was performed. RESULTS: Corneal abrasion caused by vegetable matter was the main predisposing factor. Stromal infiltration was observed in 12 patients. Six patients did not response to medical treatment, requiring surgical care, including two enucleations surgery. Fusarium solani (n = 6) and Fusarium dimerum (n = 4) were the main fungal species involved in fungal keratitis. Clinical failures were more prevalent with F. solani infections. The lowest minimal inhibitory concentrations for Fusarium sp. were observed with voriconazole and amphotericin B. CONCLUSION: In Reunion Island, the epidemiology of fungal keratitis is characterized by the predominance of Fusarium species, potentially involved in visual loss. This pattern is consistent with the epidemiology usually observed in tropical areas.

Candidemia in the intensive care unit: A 12-year retrospective cohort study in Reunion Island.

OBJECTIVES: We aimed to describe the epidemiology of Candida bloodstream infection in an intensive care unit (ICU) in Reunion Island. METHODS: We performed a retrospective cohort study and evaluated 63 candidemia episodes, which occurred between January 2004 and December 2015 in the ICU of a University Hospital in St-Pierre. RESULTS: The incidence rate of candidemia in the ICU was estimated at 7.6%. Candida albicans was the most common yeast pathogen species recovered (54%), followed by Candida glabrata (17%), Candida tropicalis (12%) and Candida parapsilosis (10%). Between 2012 and 2015, we also observed a modification of antifungal use. CONCLUSION: The epidemiology of candidemia in Reunion Island is characterized by the predominance of Candida albicans and by the relative importance of Candida tropicalis. This pattern corresponds to a model of epidemiological transition between the one usually observed in tropical areas and the one observed in temperate countries.

From phaeohyphomycosis to disseminated chromoblastomycosis: A retrospective study of infections caused by dematiaceous fungi.

OBJECTIVE: Infections caused by dematiaceous fungi are more common in tropical and subtropical areas. We aimed to describe the clinical, microbiological and therapeutic aspects of case patients diagnosed at a University Hospital located on an Indian Ocean island. PATIENTS AND METHODS: We performed an observational retrospective study of infections caused by dematiaceous fungi diagnosed at the University Hospital of Saint-Pierre, Reunion, from 2000 to 2015. Mycological identifications were performed at the National Reference Center for Invasive Mycosis and Antifungal Agents (Paris). RESULTS: The review of clinical and microbiological data of 11 patients identified revealed that five were infected by dematiaceous fungi. Two had cutaneous phaeohyphomycosis, two had cerebral phaeohyphomycosis and one had cutaneous chromoblastomycosis with brain and potentially medullary dissemination. Skin lesions and cerebral abscesses were quite varied. CONCLUSION: Infections caused by dematiaceous fungi are rare. Medullary and brain localizations are extremely rare, especially for chromoblastomycosis. Cutaneous manifestations of phaeohyphomycosis are varied; diagnosis is thus more difficult. It is therefore important, when confronted with a chronic tumor-like lesion in endemic areas, to perform a biopsy for pathology and fungal culture. While surgical excision is not always sufficient, medical treatment of these infections is not standardized, but relies on an azole, which can be associated with another antifungal agent.

Validation of a viral and bacterial inactivation step during the extraction and purification process of porcine collagen.

In the last few years, regulations for biomolecule production, and especially for extraction and purification of animal molecules such as collagen, have been reinforced to ensure the sanitary safety of the materials. To be authorized to market biomaterials based on collagen, manufacturers now have to prove that at least one step of their process is described in guidelines to inactivate prion, viruses, and bacteria. The present study focuses on the inactivation step performed during the extraction and purification of porcine type I atelocollagen. We chose to determine the reduction factor of a 1 M NaOH step on porcine parvovirus and four bacterial strains inactivation. During the extraction step, we deliberately inoculated the collagen suspension with the different microorganisms tested. Then, 1 M NaOH was added to the suspension for 1 hour at 20 degrees C. We demonstrated that this treatment totally inactivated S. aureus, P. aeruginosa, C. albicans and A. niger which are bacterial strains responsible of severe human pathology. The reduction factors reached more than 4 logs for B. cereus spores and 4 logs for the porcine parvovirus. are encouraging as those two microorganisms are known to be very resistant to inactivation.

Surveillance of carbapenemase-producing Enterobacteriaceae in the Indian Ocean Region between January 2010 and December 2015.

BACKGROUND: The aim of this study was to trace the emergence of carbapenemase-producing Enterobacteriaceae (CPE) on Reunion Island, a French overseas territory well suited for the surveillance of CPE emergence in patients from the entire Indian Ocean Region. METHODS: This retrospective multicenter study was conducted on Reunion Island between 2010 and 2015. RESULTS: A total of 43 CPEs were isolated during the course of the study, in 36 patients (50% in the last year alone). Among these patients, 21 had a link with a foreign country (58%), mainly Mauritius (47.6%). Over the same period, CPEs were isolated from 13 of 1735 (0.7%) repatriated patients to Reunion Island from another country of the Indian Ocean Region. The incidence of isolation of CPEs in the repatriated patients treated in Mauritius was higher (9.2%) than in patients treated in Madagascar or the Comoros Islands (<1%, P<0.001). The most commonly isolated microorganism was Klebsiella pneumoniae (39.5%). The most frequently identified carbapenemase was NDM-1 (81.4%); 100% and 56% of the NDM-1 strains were susceptible to tigecycline and colistin, respectively. In-hospital mortality rate was higher in patients presenting with CPE infection than in patients without CPE infection (75% vs. 25%, P=0.04). CONCLUSION: As elsewhere in the world, the number of CPE cases on Reunion Island is on the rise. Most cases involve patients from Mauritius, which justifies screening and isolating CPE in patients from that country.

[Apoptosis and programmed cell death. Host parasite relationship new paradigm]. / Apoptose et mort cellulaire programmée, un nouveau paradigme de la relation hôte/parasite.

Apoptosis and programmed cell death are amongst the most fascinating new concepts for understanding the host-parasite relationship. A growing body data is raising questions about the impact of the death of an individual parasite on the survival of the parasite population as a whole. Does the parasite induce the death of the host cell as an expression of virulence or does it inhibit that death as a factor for transmissibility? Current evidence that these effects are mediated through specific highly regulated mechanisms suggest that deciphering programmed cell death could provide new tools for control of parasitic diseases.

[Outsourced real-time PCR diagnosis of cutaneous leishmaniasis in the outbreak region of Constatine, Algeria]. / Diagnostic delocalise par PCR temps réel de la leishmaniose cutanée sévissant dans le foyer de Constantine (Algérie).

Taking into account the re-emergence of leishmaniasis in the world, the geographic variability of its epidemiology and the growing numbers of travellers, a pilot study on the diagnosis of cutaneous leishmaniasis was undertaken in Constatine, one of the outbreak regions in eastern Algeria. A total of 143 specimens were collected on blotters and tested by real-time PCR. Results were compared with those of direct examination. Diagnosis was positive for leishmaniasis in 81% of cases using PCR versus 48% of cases using microscopy. Real-time PCR showed a significant quantitative difference between patients for whom microscopic diagnosis was positive and those for whom direct examination was negative. The results presented in this study demonstrated the effectiveness and sensitivity of PCR in the diagnosis of cutaneous leishmaniasis from blotter specimens. This technique enabled in-field collection of specimens from each patient and provided prompt results. North-South cooperation based on the use of simple means for transmission of specimens for molecular diagnosis allowed creation of an effective partnership for daily diagnosis and promoted exchange between investigators in preparation for technology transfer.

[Is Plasmodium vivax still a paradigm for uncomplicated malaria?]. / Plasmodium vivax est-il encore le paradigme d'un paludisme simple?

P. vivax is supposed to be involved in benign tertian fever, responsible for a non-complicated disease that could be easily treated by standard antimalarial drug regimen. This could be considered as a long-standing paradigm of a non-virulent malaria parasite. When a patient exhibits severe malaria with the vivax parasite, the issue is often to find falciparum. However, with the implementation of molecular diagnosis, it has becoming more evident that vivax parasites could be involved in severe disease with probably a different pathogenesis. Mixed infections are frequent in various parts of Southeast Asian endemic areas and it was speculated that drugs used to treat falciparum could be involved in the development of vivax drug resistance. How should primaquine be used today for the treatment and prophylaxis of vivax malaria? Considering the re-emergence of vivax malaria in several areas, improving the treatment for this disease is certainly an important issue to avoid late episodes and transmission potential.

[Antimicrobial resistance of Streptococcus pneumoniae strains isolated in the Reunion Island during 2004]. / Résistance aux antibiotiques de Streptococcus pneumoniae à la Réunion en 2004.

OBJECTIVE AND METHOD: Available data from the Southern Reunion Island Medical Group was processed to assess the evolution of Streptococcus pneumoniae resistance to antibiotics since 1994 when the first penicillin-non-susceptible S. pneumoniae (PNSSP) was identified. In addition, 249 strains, isolated between 1998 and 2004, were tested against telithromycin and moxifloxacin. RESULTS: Between 1994 and 2004, the percentage of PNSSP increased from 0 to 59.2%. Among PNSSP, 13.9% were resistant strains in 2004 with MICs<4 microg/ml. Before 2001 the rate of resistance to penicillin was superior to 50%. In 2004, 15.8 and 8.7% of the isolated strains were of decreased susceptibility to amoxicillin and cefotaxime respectively while none were resistant to either treatment. Other antibiotics followed the pattern of resistance to penicillin. Between 1998 and 2004, resistance to erythromycin decreased from 42.5 to 35.1%, from 35.1 to 22.8% for cyclins, from 18.8 to 8.8 for chloramphenicol, and from 38.3 to 12.3% for cotrimoxazole. All tested strains were susceptible to both telithromycin and moxifloxacin. CONCLUSION: Amoxicillin remains efficient for all strains isolated in the Reunion Island in 2004. The presence of strains with decreased susceptibility to third generation cephalosporins implies combination with vancomycin for empirical treatment of pneumococcal meningitis. Moxifloxacin can be used when using a fluoroquinolone is justified. Telithromycin is efficient even on strains resistant to erythromycin and consequently this molecule can be prescribed in the case of a required macrolide treatment.

Helicobacter pylori resistance to clarithromycin in Reunion Island.

OBJECTIVE: The increasing resistance of Helicobacter pylori to clarithromycin led to developing new eradication treatment regimens. The objective of our observational study was to determine the proportion of H. pylori strains resistant to clarithromycin in infected patients in Reunion Island and to suggest a first-line treatment in agreement with the local ecology. PATIENTS AND METHODS: We included 200 patients who underwent esophagogastroduodenoscopy at the University Hospital of Saint-Pierre from February to July 2014. H. pylori was isolated from 73 patients. RESULTS: A wild-type susceptibility profile to clarithromycin was observed in 64 isolates (87.7%) and nine isolates (12.3%) had a resistant mutation profile. CONCLUSION: With a proportion of resistant strains below the critical threshold of 15%, physicians in Reunion Island may continue to prescribe the usual treatment regimen as a first-line option (clarithromycin, amoxicillin, and proton pump inhibitor for 14 days).

Absence of nucleotide polymorphism in a Plasmodium vivax multidrug resistance gene after failure of mefloquine prophylaxis in French Guyana.

Vivax malaria is widespread and resistance has been described for chloroquine and sulfadoxine-pyrimethamine. We report on evidence of failure of mefloquine prophylaxis in a French soldier who contracted Plasmodium vivax in French Guyana, South America. Despite regular weekly mefloquine prophylaxis (250 mg/d), the patient presented with a first episode of vivax malaria, which was treated by chloroquine alone, then experienced a second crisis in France. The reappearance of the parasites occurred one day after the end of prophylaxis, confirming parasitological and clinical resistance in a non-immune patient. Mefloquine was detected by a liquid chromatography assay in plasma at a level of 1062 ng/ml, which was higher than the expected concentration after five months of weekly prophylaxis. This isolate had no single nucleotide polymorphisms of the pvmdr1 gene at seven allele positions: pvmdr1 N91, Y189, Y976, S1071, F1076, N1079 and D1291, corresponding to codons 86, 184, 939, 1034, 1039, 1042 and 1246 in P. falciparum. This observation of failure of mefloquine prophylaxis against P. vivax, when added to previously reported chloroquine and atovaquone-proguanil failure, strengthens the case for re-evaluating drug policies for vivax malaria and the need for continuous research on molecular markers of drug resistance.

Acute appendicitis in an incarcerated crural hernia: analysis of our experience.

INTRODUCTION: The finding of the vermiform appendix within a crural hernia (Amyand s hernia) is a rare entity whose incidence is not described in the literature. OBJECTIVE: The aim of this study was to report our hospital s experience in this kind of pathology. MATERIAL AND METHODS: Between 1993 and 2004, 4,572 acute appendicitis and 372 incarcerated crural hernia cases have been operated on in our hospital. We studied 6 cases of incarcerated crural hernia with vermiform appendix inside. We analyzed in retrospect the following parameters: age, sex, personal history, clinical manifestations, preoperative diagnosis, surgical technique, mean hospital stay, and outcome. RESULTS: All patients were women with a mean age of 78.8 years. Most frequent clinical manifestations included pain and a mass in the right inguinocrural region, of variable intensity and duration. No clinical, laboratory, or radiographic signs help in reaching a correct preoperative diagnosis. General anesthesia and a crural approach are used in most surgical operations. In all cases an appendectomy was performed via the hernia sac, thus proving the presence of acute appendicitis in four of them (66.67%). A prosthetic mesh was used in 3 cases, and one case of wound infection was found. In the other cases we sutured the hernia ring using prolene. CONCLUSION: The finding of the appendix in an incarcerated crural hernia is a rare entity in old women that is difficult to diagnose preoperatively. Treatment includes appendectomy and herniorraphy. The use of prosthetic mesh is controversial.

[Lymphocytis meningitis: Listeria monocytogenes is a potential risk in a immunocompetent child]. / Méningite lymphocytaire: Listeria monocytogenes, une étiologie à ne pas négliger chez l'enfant immunocompétent.

UNLABELLED: Meningoencephalitis due to Listeria monocytogenes is a rare and serious form of brainstem infection in childhood. OBSERVATION: We report the case of a 7 year-old girl presenting lymphocytic meningitis with a high CRP level. Parenteral antibiotics combining ceftriaxone and vancomycine led initially to clinical improvement. Ten days later, secondary brainstem inflammation with hydrocephalus appeared and led to the detection of L. monocytogenes during external ventricular bypass. CONCLUSION: This observation of paediatric lymphocytic meningoencephalitis suggests a prescription of amoxicillin in association with first line antibiotics, particularly when an important inflammatory syndrome exists, immunocompetent children included.

Primary cutaneous melanoma in hidden sites is associated with thicker tumours - a study of 829 patients.

The aim of this study was to determine if primary cutaneous melanomas in hidden anatomical sites were associated with thicker tumours. Retrospective medical data of 829 patients with melanomas diagnosed at our centre between January 1976 and July 1998 were recorded from our database. Three groups were defined according to the anatomical site of the primary melanoma: (1) visible areas (group 1: 493 patients); (2) visible areas only to the patients or to their partners in privacy (group 2: 281 patients); and (3) hidden areas (group 3: 55 patients). Univariate analysis indicated that patients with melanoma in hidden regions presented significantly thicker tumours (median for group 3: 2.25 versus 1.17 for group 1 and 1.42 for group 2). This group were also more commonly males (group 3: 58% men versus group 1: 38% and group 2: 51%), in a more advanced stage (metastatic disease at diagnosis in 16% of patients in group 3 versus 6% in groups 1 and 2) and at a more advanced age (median group 3: 66 years versus group 1: 59 years and group 2: 51 years), than patients in the other two groups. The association between tumour thickness and body site remained statistically significant after a multivariate analysis. As a delay in diagnosis may be responsible for the thicker size of melanoma in the hidden areas, preventive programmes should stress the importance of not forgetting these locations in self-examination and screening. Special attention should be given to educating elderly men.