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.

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.

[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.

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.

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).

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.

[Molecular diagnosis by real-time PCR of Leishmania isolated from the Phlebotomus vector]. / Diagnostic moléculaire par PCR en temps réel des leishmanies isolées à partir du vecteur (Phlebotomus).

The authors report the demonstration of Leishmania in the tissue of Phlebotomus samples captured in the region of Constantine in 2010. The four species that could be identified were: Phlebotomus larroussius, P. perfiliewi, P. longicuspis, and Sergentomyia minuta.

[Utility of real-time PCR for the diagnosis of infantile visceral leishmaniasis in Algeria]. / Contribution de la PCR en temps réel au diagnostic de la leishmaniose viscérale infantile en Algérie.

Visceral leishmaniasis (VL) is a parasitic disease and serious public health problem. The most severe form of all leishmaniases, it is fatal if untreated. Currently, it affects close to 540 people per year in Algeria, mainly in Kabylie, where it is fatal in 6% of all cases. This disease primarily affects children. Its diagnosis is based principally on visualization of parasites in bone marrow aspirate. Serologic studies are also used to diagnose VL, as is molecular biology, which has been demonstrated to be both faster and more sensitive. The aim of our study was to evaluate the utility of real-time polymerase chain reaction (RT-PCR) in the diagnosis of VL in endemic areas. Of the 108 samples analyzed, 32 were positive according to RT-PCR (29.6%); microscopy yielded positive result in 24% and serology in 25.9%. RT-PCR increased the overall number of diagnoses detected from 26 to 32, a 20% improvement over microscopic methods. In view of the lethal consequences of failure to diagnose this disease, any improvement in diagnostic methods provides direct medical benefit.

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.

[Determinants of group B streptococcus maternal colonization and factors related to its vertical perinatal transmission: case-control study]. / Déterminants de la colonisation maternelle à streptocoque B et facteurs associés à sa transmission verticale périnatale: étude cas-témoins.

OBJECTIVES: To investigate the determinants of Group B streptococcus (GBS) maternal colonization, as well as factors associated with its vertical transmission. PATIENTS AND METHODS: Case-control study on all singletons pregnancies delivered beyond at least 24 weeks of amenorrhoea in Southern Reunion maternities for which GBS screening was known. Multiple logistic regression analysis using 2004-2007 dataset of South Reunion birth registers. RESULTS: Out of 17,430 women delivered between 1st January 2004 and 31st December 2007, 2911 (16.7%) carried GBS. In a model adjusted on antenatal care, risk groups for GBS carriage were the women indigenous from another island of the Indian Ocean than Reunion (OR: 1.29, CI95%: 1.05-1.57) and obese women (body mass index ≥ 30, OR: 1.19, CI95%: 1.03-1.18). Protective factors included birthplace in mainland France (OR: 0.82, CI95%: 0.69-0.97) and underweight (OR: 0.81; CI95%: 0.69-0. 95). In a model controlling for a composite obstetrical variable delineating the protective roles of C-section and antibioprophylaxis as well as the putative role of meconium-stained fluids (thin, thick or fetid), all previously found in our setting, three key factors were independently associated with GBS vertical mother-to-child transmission: obesity (OR: 1.48, CI95%: 1.05-2.09), fetal tachycardia (OR: 4.92, CI95%: 2.79-8.68) and late preterm birth (35 to 36 wks, OR: 2.14, CI95%: 1.32-3.45). CONCLUSION: These findings strengthen the putative roles of corpulence and ethnicity in GBS acquisition previously found in the United States, while confirming an authentic role of obesity in its vertical transmission, independently of other classical cofactors lighted by our study.

Maxillary sinus fungal infection by Acremonium.

OBJECTIVE: To illustrate by this case report that Acremonium must now be considered as a differential diagnosis in cases of maxillary fungus balls. CASE REPORT: Seventy-seven-year-old woman consulted for persistent pain of the right maxillary sinus, with rhinorrhea and nocturnal coughing. Computed tomography (CT) of the sinuses showed a heterogeneous opacification of the right maxillary sinus with well-defined hyperdense foci suggesting aspergillosis. She underwent a middle meatus antrectomy by an endonasal approach. Six months after the surgery, her symptoms were gone and had not recurred. Mycological examination found Acremonium. DISCUSSION/CONCLUSION: Acremonium is a genus of saprobic fungi that rarely cause disease in humans. Infection with Acremonium has recently been described in immunocompromised patients. We describe the first case of fungal maxillary sinusitis caused by Acremonium in an immunocompetent person. Clinically and radiologically, the initial diagnosis was aspergillosis. Acremonium must be considered together with aspergillosis in all situations of fungus ball chronic sinusitis.

[Evolution of resistance to antibiotics from 1997 to 2005 in the Reunion Island]. / Évolution de la résistance aux antibiotiques de 1997 à 2005 à la Réunion.

OBJECTIVE: The groupe hospitalier Sud Reunion (GHSR) is a 1130-bed hospital center, located on the Reunion Island, (Indian Ocean). We studied the profiles of antibiotic resistance in 2005, and compared those with previous data collected in 1997-1998, and with Metropolitan France and European data. MATERIAL AND METHODOLOGY: All bacteriological strains isolated from diagnostic samples in 2005 were analyzed according to CA-SFM recommendations. RESULTS: Since 1997, the rates of resistance to enterobacteria (betalactam, aminoside, quinolone, trimethoprim-sulfamethoxazole), Pseudomonas aeruginosa (ticarcillin, amikacin, ciprofloxacin, fosfomycin), Acinetobacter baumanii (amikacin) has decreased significantly. The rate of methicillin-resistant Staphylococcus aureus (1997: 3.6 %, 2005: 13.4 %) has increased but less than in Metropolitan France. The rate of Streptococcuspneumonia with decreased susceptibility to penicillin has increased (1997: 25.5 %, 2005: 42.9 %), as for Haemophilusinfluenzae which present an important increase of betalactam resistance (1997: 15.5 %, 2005: 37.8 %). CONCLUSION: By comparing our data to 1997 and Metropolitan French data, it seems that the GHSR has managed to protect its hospital-based microbial ecology. However, community germs showed increasing resistance, probably because of an increasing antibiotic pressure, but with resistance rates often inferior to Metropolitan French ones.

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.

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.

Toxoplasma gondii: comparison of human CD34+ and monocyte-derived dendritic cells after parasite infection.

Human dendritic cells (DC) obtained in vitro from CD34(+) progenitors (CD34-DC) or blood monocytes (mo-DC) are different DC which may be used in a model of T. gondii infection. We compared the survival, infection rate and cell surface receptor expression of both DC types after living T. gondii tachyzoite infection. CD34-DC appeared less resistant to the parasite than mo-DC. At 48h post-infection, chemokine receptors responsible for DC homing and migration were absent in mo-DC, while down regulation of CCR6 and up regulation of CCR7 was observed in CD34-DC. This result, suggesting migration ability of CD34-DC, was confirmed by in vitro migration experiments against different chemokines. Tachyzoite supernatant, used as chemokine, attracted immature CD34-DC as observed by MIP3alpha, while MIP3beta, as expected, attracted mature CD34-DC. Under similar conditions, no significant difference was noticed between mature or immature mo-DC. These data indicated that CD34-DC represent an alternative model that allows migration assay of infected DC by T. gondii.