Awareness of HIV Testing Guidelines Is Low among Swiss Emergency Doctors: A Survey of Five Teaching Hospitals in French-Speaking Switzerland.

BACKGROUND: In Switzerland, 30% of HIV-infected individuals are diagnosed late. To optimize HIV testing, the Swiss Federal Office of Public Health (FOPH) updated 'Provider Induced Counseling and Testing' (PICT) recommendations in 2010. These permit doctors to test patients if HIV infection is suspected, without explicit consent or pre-test counseling; patients should nonetheless be informed that testing will be performed. We examined awareness of these updated recommendations among emergency department (ED) doctors. METHODS: We conducted a questionnaire-based survey among 167 ED doctors at five teaching hospitals in French-Speaking Switzerland between 1(st) May and 31(st) July 2011. For 25 clinical scenarios, participants had to state whether HIV testing was indicated or whether patient consent or pre-test counseling was required. We asked how many HIV tests participants had requested in the previous month, and whether they were aware of the FOPH testing recommendations. RESULTS: 144/167 doctors (88%) returned the questionnaire. Median postgraduate experience was 6.5 years (interquartile range [IQR] 3; 12). Mean percentage of correct answers was 59 ± 11%, senior doctors scoring higher (P=0.001). Lowest-scoring questions pertained to acute HIV infection and scenarios where patient consent was not required. Median number of test requests was 1 (IQR 0-2, range 0-10). Only 26/144 (18%) of participants were aware of the updated FOPH recommendations. Those aware had higher scores (P=0.001) but did not perform more HIV tests. CONCLUSIONS: Swiss ED doctors are not aware of the national HIV testing recommendations and rarely perform HIV tests. Improved recommendation dissemination and adherence is required if ED doctors are to contribute to earlier HIV diagnoses.

An analysis of the benefit of using HEV genotype 3 antigens in detecting anti-HEV IgG in a European population.

BACKGROUND: The benefit of using serological assays based on HEV genotype 3 in industrialised settings is unclear. We compared the performance of serological kits based on antigens from different HEV genotypes. METHODS: Taking 20 serum samples from patients in southwest France with acute HEV infection (positive PCR for HEV genotype 3) and 550 anonymised samples from blood donors in southwest Switzerland, we tested for anti-HEV IgG using three enzyme immunoassays (EIAs) (MP Diagnostics, Dia.Pro and Fortress) based on genotype 1 and 2 antigens, and one immunodot assay (Mikrogen Diagnostik recomLine HEV IgG/IgM) based on genotype 1 and 3 antigens. RESULTS: All acute HEV samples and 124/550 blood donor samples were positive with ≥1 assay. Of PCR-confirmed patient samples, 45%, 65%, 95% and 55% were positive with MP Diagnostics, Dia.Pro, Fortress and recomLine, respectively. Of blood donor samples positive with ≥1 assay, 120/124 (97%), were positive with Fortress, 19/124 (15%) were positive with all EIAs and 51/124 (41%) were positive with recomLine. Of 11/20 patient samples positive with recomLine, stronger reactivity for HEV genotype 3 was observed in 1/11(9%), and equal reactivity for both genotypes in 5/11 (45.5%). CONCLUSIONS: Although recomLine contains HEV genotype 3, it has lower sensitivity than Fortress in acute HEV infection and fails to identify infection as being due to this genotype in approximately 45% of patients. In our single blood donor population, we observe wide variations in measured seroprevalence, from 4.2% to 21.8%, depending on the assay used.

Performance of noninvasive ventilation algorithms on ICU ventilators during pressure support: a clinical study.

To evaluate the impact of noninvasive ventilation (NIV) algorithms available on intensive care unit ventilators on the incidence of patient-ventilator asynchrony in patients receiving NIV for acute respiratory failure. Prospective multicenter randomized cross-over study. Intensive care units in three university hospitals. Patients consecutively admitted to the ICU and treated by NIV with an ICU ventilator were included. Airway pressure, flow and surface diaphragmatic electromyography were recorded continuously during two 30-min periods, with the NIV (NIV+) or without the NIV algorithm (NIV0). Asynchrony events, the asynchrony index (AI) and a specific asynchrony index influenced by leaks (AIleaks) were determined from tracing analysis. Sixty-five patients were included. With and without the NIV algorithm, respectively, auto-triggering was present in 14 (22%) and 10 (15%) patients, ineffective breaths in 15 (23%) and 5 (8%) (p = 0.004), late cycling in 11 (17%) and 5 (8%) (p = 0.003), premature cycling in 22 (34%) and 21 (32%), and double triggering in 3 (5%) and 6 (9%). The mean number of asynchronies influenced by leaks was significantly reduced by the NIV algorithm (p < 0.05). A significant correlation was found between the magnitude of leaks and AIleaks when the NIV algorithm was not activated (p = 0.03). The global AI remained unchanged, mainly because on some ventilators with the NIV algorithm premature cycling occurs. In acute respiratory failure, NIV algorithms provided by ICU ventilators can reduce the incidence of asynchronies because of leaks, thus confirming bench test results, but some of these algorithms can generate premature cycling.

Awareness of human immunodeficiency virus screening guidelines is low in emergency departments of western Switzerland.

Background: Human immunodeficiency virus (HIV) prevalence in Switzerland is 0.4% and 30% of HIV patients are diagnosed with CD4 counts <200 cells/microliter. In 2010, the Swiss Federal Office of Public Health (SFOP) published updated guidelines regarding Physician- Initiated Counseling and Testing (PICT) for HIV. In the new guidelines, when acute HIV infection is suspected or HIV is among the differential diagnoses, an HIV test is performed without risk assessment nor prior counseling, unless the patient specifically refuses it. Counseling and verbal consent are still required when the patient asks for an HIV test or belongs to a high risk group. Whist HIV testing in the emergency departments (ED) is recommended, only 1% of patients are currently screened. Lack of awareness among physicians has been cited in the literature as the first barrier to guideline implementation. Objectives: To test if physicians working in EDs of 5 large teaching hospitals in western Switzerland, admitting 175,000 patients / year, were aware of the updated SFOP guidelines. Methods: A survey was delivered to 167 ED physicians in the summer of 2011. The survey consisted of 26 vignettes designed to test whether physicians would request an HIV test according to the new guidelines and if they knew when the PICT strategy was allowed or counseling required. Finally, physicians were asked the number of HIV tests they had requested in the previous 4 weeks, and if they were aware of the new HIV guidelines. Results are presented as mean and standard deviation, median and interquartile range (IQR), or as proportions; Student's t test was used to compare continuous variables; Results: 143 physicians returned the survey (86%); mean age was 32 ± 8 years, and median postgraduate experience of 6 years (IQR 3-12); 52% were male and 17% were attendings. The percentage of correct responses was 60 ± 13% with no difference between attendings and residents (p = 0.31); 2 of the 3 questions with the lowest scores were failure to recognize situations in which HIV testing was indicated, and the third one a failure to recognize acute HIV infection. 82% of physicians were not aware of the new guidelines. The median number of test requests was 1 (IQR 0-2, range 1-10). Conclusion: ED physicians are not aware of current HIV screening guidelines published by the SFOP, and rarely perform HIV tests. An information campaign is required if ED physicians are expected to play a significant role in the reduction of undiagnosed HIV patients.

Pneumolysin Activates the NLRP3 Inflammasome and Promotes Proinflammatory Cytokines Independently of TLR4.

Pneumolysin (PLY) is a key Streptococcus pneumoniae virulence factor and potential candidate for inclusion in pneumococcal subunit vaccines. Dendritic cells (DC) play a key role in the initiation and instruction of adaptive immunity, but the effects of PLY on DC have not been widely investigated. Endotoxin-free PLY enhanced costimulatory molecule expression on DC but did not induce cytokine secretion. These effects have functional significance as adoptive transfer of DC exposed to PLY and antigen resulted in stronger antigen-specific T cell proliferation than transfer of DC exposed to antigen alone. PLY synergized with TLR agonists to enhance secretion of the proinflammatory cytokines IL-12, IL-23, IL-6, IL-1β, IL-1α and TNF-α by DC and enhanced cytokines including IL-17A and IFN-γ by splenocytes. PLY-induced DC maturation and cytokine secretion by DC and splenocytes was TLR4-independent. Both IL-17A and IFN-γ are required for protective immunity to pneumococcal infection and intranasal infection of mice with PLY-deficient pneumococci induced significantly less IFN-γ and IL-17A in the lungs compared to infection with wild-type bacteria. IL-1β plays a key role in promoting IL-17A and was previously shown to mediate protection against pneumococcal infection. The enhancement of IL-1β secretion by whole live S. pneumoniae and by PLY in DC required NLRP3, identifying PLY as a novel NLRP3 inflammasome activator. Furthermore, NLRP3 was required for protective immunity against respiratory infection with S. pneumoniae. These results add significantly to our understanding of the interactions between PLY and the immune system.

Sterblichkeit während Grippeepidemien in der Schweiz 1969-1985. [Mortality in influenza epidemics in Switzerland 1969-1985].

In Switzerland from 1969-1985, 9 out of 11 influenza epidemics were associated with a statistically significant increase in mortality. A total of 12,202 excess deaths from all causes was identified. Expected deaths were forecast for each epidemic period separately for 4 age groups using Fourier and Arima modeling. 75.7% of all-cause excess deaths occurred in age group 70 to 89 and 5.1% in age group 1-59. In the 70-89 years old group the excess mortality risk during influenza epidemics was 271.6 per 100,000, whereas in age group 1-59 it was only 1.7 per 100,000. Only 40% of all excess deaths had been ascribed to acute respiratory conditions. Influenza viruses A H3N2 were the most frequently identified agents. In some instances mortality increased before the morbidity reports of the Swiss practitioners indicated the occurrence of an epidemic. Also, morbidity reporting decreased over successive years. A decrease in mortality following the epidemics was not observed. A more complete vaccination of high risk patients in Switzerland is desirable.

A prospective, randomized, and controlled study of fluid management in children with severe head injury: lactated Ringer's solution versus hypertonic saline.

OBJECTIVES: Resuscitation in severe head injury may be detrimental when given with hypotonic fluids. We evaluated the effects of lactated Ringer's solution (sodium 131 mmol/L, 277 mOsm/L) compared with hypertonic saline (sodium 268 mmol/L, 598 mOsm/L) in severely head-injured children over the first 3 days after injury. DESIGN: An open, randomized, and prospective study. SETTING: A 16-bed pediatric intensive care unit (ICU) (level III) at a university children's hospital. PATIENTS: A total of 35 consecutive children with head injury. INTERVENTIONS: Thirty-two children with Glasgow Coma Scores of <8 were randomly assigned to receive either lactated Ringer's solution (group 1) or hypertonic saline (group 2). Routine care was standardized, and included the following: head positioning at 30 degrees; normothermia (96.8 degrees to 98.6 degrees F [36 degrees to 37 degrees C]); analgesia and sedation with morphine (10 to 30 microg/kg/hr), midazolam (0.2 to 0.3 mg/kg/hr), and phenobarbital; volume-controlled ventilation (PaCO2 of 26.3 to 30 torr [3.5 to 4 kPa]); and optimal oxygenation (PaO2 of 90 to 105 torr [12 to 14 kPa], oxygen saturation of >92%, and hematocrit of >0.30). MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure and intracranial pressure (ICP) were monitored continuously and documented hourly and at every intervention. The means of every 4-hr period were calculated and serum sodium concentrations were measured at the same time. An ICP of 15 mm Hg was treated with a predefined sequence of interventions, and complications were documented. There was no difference with respect to age, male/female ratio, or initial Glasgow Coma Score. In both groups, there was an inverse correlation between serum sodium concentration and ICP (group 1: r = -.13, r2 = .02, p < .03; group 2: r = -.29, r2 = .08, p < .001) that disappeared in group 1 and increased in group 2 (group 1: r = -.08, r2 = .01, NS; group 2: r = -.35, r2 =.12, p < .001). Correlation between serum sodium concentration and cerebral perfusion pressure (CPP) became significant in group 2 after 8 hrs of treatment (r = .2, r2 = .04, p = .002). Over time, ICP and CPP did not significantly differ between the groups. However, to keep ICP at <15 mm Hg, group 2 patients required significantly fewer interventions (p < .02). Group 1 patients received less sodium (8.0 +/- 4.5 vs. 11.5 +/- 5.0 mmol/kg/day, p = .05) and more fluid on day 1 (2850 +/- 1480 vs. 2180 +/- 770 mL/m2, p = .05). They also had a higher frequency of acute respiratory distress syndrome (four vs. 0 patients, p = .1) and more than two complications (six vs. 1 patient, p = .09). Group 2 patients had significantly shorter ICU stay times (11.6 +/- 6.1 vs. 8.0 +/- 2.4 days; p = .04) and shorter mechanical ventilation times (9.5 +/- 6.0 vs. 6.9 +/- 2.2 days; p = .1). The survival rate and duration of hospital stay were similar in both groups. CONCLUSIONS: Treatment of severe head injury with hypertonic saline is superior to that treatment with lactated Ringer's solution. An increase in serum sodium concentrations significantly correlates with lower ICP and higher CPP. Children treated with hypertonic saline require fewer interventions, have fewer complications, and stay a shorter time in the ICU.

End-tidal carbon dioxide monitoring using a naso-buccal sensor is not appropriate to monitor capnia during non-invasive ventilation.

BACKGROUND: In acute respiratory failure, arterial blood gas analysis (ABG) is used to diagnose hypercapnia. Once non-invasive ventilation (NIV) is initiated, ABG should at least be repeated within 1 h to assess PaCO2 response to treatment in order to help detect NIV failure. The main aim of this study was to assess whether measuring end-tidal CO2 (EtCO2) with a dedicated naso-buccal sensor during NIV could predict PaCO2 variation and/or PaCO2 absolute values. The additional aim was to assess whether active or passive prolonged expiratory maneuvers could improve the agreement between expiratory CO2 and PaCO2. METHODS: This is a prospective study in adult patients suffering from acute hypercapnic respiratory failure (PaCO2 ≥ 45 mmHg) treated with NIV. EtCO2 and expiratory CO2 values during active and passive expiratory maneuvers were measured using a dedicated naso-buccal sensor and compared to concomitant PaCO2 values. The agreement between two consecutive values of EtCO2 (delta EtCO2) and two consecutive values of PaCO2 (delta PaCO2) and between PaCO2 and concomitant expiratory CO2 values was assessed using the Bland and Altman method adjusted for the effects of repeated measurements. RESULTS: Fifty-four datasets from a population of 11 patients (8 COPD and 3 non-COPD patients), were included in the analysis. PaCO2 values ranged from 39 to 80 mmHg, and EtCO2 from 12 to 68 mmHg. In the observed agreement between delta EtCO2 and deltaPaCO2, bias was -0.3 mmHg, and limits of agreement were -17.8 and 17.2 mmHg. In agreement between PaCO2 and EtCO2, bias was 14.7 mmHg, and limits of agreement were -6.6 and 36.1 mmHg. Adding active and passive expiration maneuvers did not improve PaCO2 prediction. CONCLUSIONS: During NIV delivered for acute hypercapnic respiratory failure, measuring EtCO2 using a dedicating naso-buccal sensor was inaccurate to predict both PaCO2 and PaCO2 variations over time. Active and passive expiration maneuvers did not improve PaCO2 prediction. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01489150.

Nontypable Haemophilus influenzae displays a prevalent surface structure molecular pattern in clinical isolates.

Non-typable Haemophilus influenzae (NTHi) is a Gram negative pathogen that causes acute respiratory infections and is associated with the progression of chronic respiratory diseases. Previous studies have established the existence of a remarkable genetic variability among NTHi strains. In this study we show that, in spite of a high level of genetic heterogeneity, NTHi clinical isolates display a prevalent molecular feature, which could confer fitness during infectious processes. A total of 111 non-isogenic NTHi strains from an identical number of patients, isolated in two distinct geographical locations in the same period of time, were used to analyse nine genes encoding bacterial surface molecules, and revealed the existence of one highly prevalent molecular pattern (lgtF+, lic2A+, lic1D+, lic3A+, lic3B+, siaA−, lic2C+, ompP5+, oapA+) displayed by 94.6% of isolates. Such a genetic profile was associated with a higher bacterial resistance to serum mediated killing and enhanced adherence to human respiratory epithelial cells.

Evaluation of a PCR multiplex for detection and differentiation of Mycoplasma synoviae, M. gallisepticum, and M. gallisepticum strain F-vaccine

Mycoplasma gallisepticum (MG) and Mycoplasma synoviae (MS) are the mycoplasma infections of most concern for commercial poultry industry. MG infection is commonly designated as chronic respiratory disease (CRD) of chickens and infections sinusitis of turkeys. MS causes sub clinical upper respiratory infection and tenosynovitis or bursitis in chickens and turkeys. The multiplex PCR was standardized to detect simultaneously the MS, MG field strains and MG F-vaccine strain specific. The generic PCR for detection of any species of Mollicutes Class was performed and compared to the multiplex PCR and to PCR using species-specific primers. A total of 129 avian tracheal swabs were collected from broiler-breeders, layer hens and broilers in seven different farms and were examined by multiplex PCR methods. The system (multiplex PCR) demonstrated to be very rapid, sensitive, and specific. Therefore, the results showed a high prevalence of MS in the flocks examined (27.9%), and indicate that the MS is a recurrent pathogen in Brazilian commercial poultry flocks.

Genetic variability of hepatitis A virus isolates in Rio de Janeiro: implications for the vaccination of school children

The epidemiology of hepatitis A virus (HAV) infection is shifting from high to intermediate endemicity in Brazil, resulting in increased numbers of susceptible individuals and a greater potential for the emergence of outbreaks. Universal vaccination against HAV has been recommended for children, but updated sero-epidemiological data are necessary to analyze the level of natural immunity and to identify candidates for preventive measures. In addition, more molecular studies are necessary to characterize the genotypes involved in HAV infections and outbreaks. Sera from 299 school children (5-15 years old) and 25 school staff members, collected during an outbreak of HAV at a rural public school in June 2000, were tested for IgM and total anti-HAV antibodies (ELISA). Viral RNA was amplified by RT-PCR from anti-HAV IgM-positive sera and from 19 fecal samples. Direct nucleotide sequencing of the VP1/2A region was carried out on 18 PCR-positive samples. Acute HAV infection was detected by anti-HAV IgM in 93/299 children and in 3/25 adult staff members. The prevalence of total anti-HAV antibodies in IgM-negative children under 5 years of age was only 10.5%. HAV-RNA was detected in 46% IgM-positive serum samples and in 16% stool samples. Sequence analysis showed that half the isolates belonged to subgenotype IA and the other half to IB. On the basis of these data, mass vaccination against HAV is recommended without prevaccination screening, especially for children before they enter school, since nearly 90% of the children under 5 years were susceptible. Molecular characterization indicated the endemic circulation of specific HAV strains belonging to subgenotypes IA and IB.

Glomerular filtration is reduced by high tidal volume ventilation in an in vivo healthy rat model

Mechanical ventilation has been associated with organ failure in patients with acute respiratory distress syndrome. The present study examines the effects of tidal volume (V T) on renal function using two V T values (8 and 27 mL/kg) in anesthetized, paralyzed and mechanically ventilated male Wistar rats. Animals were randomized into two groups of 6 rats each: V T8 (V T, 8 mL/kg; 61.50 ± 0.92 breaths/min; positive end-expiratory pressure, 3.0 cmH2O; peak airway pressure (PAW), 11.8 ± 2.0 cmH2O), and V T27 (V T, 27 mL/kg; 33.60 ± 1.56 breaths/min; positive end-expiratory pressure, none, and PAW, 22.7 ± 4.0 cmH2O). Throughout the experiment, mean PAW remained comparable between the two groups (6.33 ± 0.21 vs 6.50 ± 0.22 cmH2O). For rats in the V T27 group, inulin clearance (mL·min-1·body weight-1) decreased acutely after 60 min of mechanical ventilation and even more significantly after 90 min, compared with baseline values (0.60 ± 0.05 and 0.45 ± 0.05 vs 0.95 ± 0.07; P < 0.001), although there were no differences between groups in mean arterial pressure or gasometric variables. In the V T8 group, inulin clearance at 120 min of mechanical ventilation remained unchanged in relation to baseline values (0.72 ± 0.03 vs 0.80 ± 0.05). The V T8 and V T27 groups did not differ in terms of serum thiobarbituric acid reactive substances (3.97 ± 0.27 vs 4.02 ± 0.45 nmol/mL) or endothelial nitric oxide synthase expression (94.25 ± 2.75 vs 96.25 ± 2.39%). Our results show that glomerular filtration is acutely affected by high tidal volume ventilation but do not provide information about the mechanism.

Epstein-Barr-viruksen antigeeniosoitustestin kehittäminen

Epstein-Barr-virus (EBV) aiheuttaa mononukleoosia eli pusutautia, joka ilmenee yleensä murrosiällä tai nuorella aikuisiällä. Mononukleoosissa on tyypilliset nielutulehduksen oireet, minkä takia sitä on vaikea erottaa muiden taudinaiheuttajien aiheuttamista nielutulehduksista. Erotusdiagnostiikan käyttö nielutulehduksessa on oleellista, koska vain Streptokokki-bakteerien aiheuttamat nielutulehdukset vaativat antibioottihoitoa. Akuutin EBV-infektion pikadiagnostiikka perustuu nykyisellään infektion seurauksena muodostuvien heterofiilisten vasta-aineiden mittaamiseen verestä. Niiden mittaamisessa on useita ongelmia, koska useilla lapsilla niitä ei muodostu lainkaan ja vanhemmillakin niitä muodostuu yleensä vasta viikon päästä mononukleoosin oireiden alkamisesta. Mittaamalla EBV:n antigeeneja saataisiin positiivinen testitulos vasta-ainetestiä nopeammin. EBV:lle ei ole kuitenkaan kehitetty antigeeniosoitustestiä todennäköisesti siksi, että EBV:n erittymisen terveiden viruksen kantajien limakalvoille uskotaan olevan ongelma antigeenitestauksessa. Diplomityön tavoitteena oli kehittää akuutin EBV-infektion pikadiagnostiikkaan soveltuva limakalvonäytteestä tehtävä immunometrinen antigeeniosoitustesti. Työssä kehitettiin uusia polyklonaalisia vasta-aineita sekä testattiin kaupallisia vasta-aineita. Vasta-aineiden toimintaa tutkittiin immunomäärityksissä kokonaista EBV:ta ja puhdistettuja proteiiniantigeeneja vastaan. Monoklonaalisten vasta-aineiden kehitys lopetettiin ennen varsinaista tuottoa, koska ensin kehitetyt polyklonaaliset vasta-aineet eivät tunnistaneet natiivia virusta vaan pelkästään immunisointeihin käytetyt rekombinanttiset kohdeproteiinit. Kaupallisista vasta-aineista yhdellä onnistuttiin kehittämään tiettävästi maailman ensimmäinen immunometrinen EBV-antigeeniosoitustesti, jossa saatiin tunnistus sekä natiivilla EBV:lla että puhdistetulla proteiiniantigeenilla. Testin herkkyys proteiiniantigeenilla oli hyvä (4 pM) ja puhdistetulla EBV-virusvalmisteellakin todennäköisesti riittävä (6,2×106 viruspartikkelia/ml) kliiniseen diagnostiikkaan. Testillä ei kuitenkaan saatu suppeasta mononukleoosipotilaiden nielunäyteaineistosta yhtään EBV-positiivista tulosta. Referenssiksi tilatut PCR-testit osoittivat näytteiden EBV-pitoisuuksien olevan liian alhaisia osoitettavaksi kehitetyllä EBV-antigeeniosoitustestillä. PCR-testauksessa mononukleoosipotilaiden nielunäytteistä osoitettujen alhaisten EBV-määrien perusteella spekuloitiin, että olisiko edustavin näytteenottopaikka akuutissa EBV-infektiossa sittenkin nielun sijaan nenänielu. Myös kirjallisuudesta löytyi tälle tukea. EBV-antigeeniosoitustestin osoitettiin toimivan hyvin standardinäyte-materiaalilla. Testikehitysprojektin jatkon kannalta oleellista on kuitenkin vielä selvittää laajemmalla kliinisellä näyteaineistolla, mistä EBV:n antigeeneja pitäisi osoittaa akuutissa EBV-infektiossa ja ovatko niiden pitoisuudet riittävän korkeita.

Caractérisation de la réponse immunitaire cellulaire dirigée contre ARFP et cartographie des épitopes du génotype 3a lors de l’infection au virus de l’hépatite C

L’interféron-α pegylé en combinaison avec la ribavirin est le seul traitement approuvé pour le traitement de l’infection au virus de l’hépatite C (VHC). L’efficacité est de 50-75%, la thérapie est coûteuse et induit beaucoup d’effets secondaires. Il est impératif d’avoir une meilleure compréhension de la pathogenèse du VHC afin de développer des traitements plus efficaces ou un vaccin. À cette fin, notre approche est de caractériser la réponse immunitaire cellulaire induite par ARFP, un antigène nouveau et conservé chez le VHC, et de cartographier les épitopes de la réponse immunitaire cellulaire d’un patient infecté au génotype 3a ayant résolu spontanément. Le génotype 3a, étant prévalant chez les utilisateurs de drogues intraveineuses (IDUs) constitue 60% des nouvelles infections. Peu d’épitopes furent identifiés auparavant pour ce génotype, ce qui rend l’étude de la réponse immunitaire difficile chez cette population. Dans cette étude, pour la réponse immunitaire cellulaire dirigée contre ARFP, nous n’avons pas observé de différence significative entre les patients ayant résolu spontanément comparativement avec ceux ayant développé une infection persistante. Ceci suggère fortement que ARFP ne joue pas un rôle majeur lors de la résolution de l’infection aigue au VHC. Pour la caractérisation de la réponse immunitaire cellulaire chez un des patients infectés au génotype 3a, nous avons identifié et caractérisé 5 épitopes spécifiquement reconnus par des lymphocytes T, CD3+, CD4+ et CD8- : E2504-521, NS31064-1081, NS4b1759-1776, NS5a2074-2091, NS5b2421-2436. Nous avons comparé avec ceux connus pour le génotype 1a. Nous avons identifié 4 nouveaux épitopes. Enfin, l’épitope NS4b1759-1776, identifié auparavant, pourrait s’avérer être un candidat intéressant dans la mise au point d’un vaccin à base de peptides immunogéniques contre le VHC.

Étude multicentrique sur les stratégies de ventilation mécanique employées chez les enfants avec un œdème pulmonaire lésionnel

Des études adultes sur l’œdème pulmonaire lésionnel et le Syndrome de Détresse Respiratoire Aiguë ont mené à l’établissement de recommandations sur les stratégies de ventilation mécanique à employer chez ces patients. Cependant, il n’est pas clair si les recommandations adultes sont également bénéfiques pour l’enfant. Objectif Décrire les stratégies de ventilation mécanique employées chez les enfants atteints d’un œdème pulmonaire lésionnel. Méthodes Étude épidémiologique transversale tenue dans 59 unités de Soins Intensifs Pédiatriques de 12 pays en Amérique du Nord et en Europe. Six jours d’étude ont eu lieu entre juin et novembre 2007. Les enfants atteints d’un œdème pulmonaire lésionnel étaient inclus et des données sur la sévérité de leur maladie, les paramètres de ventilation mécanique et les thérapies adjuvantes employées ont été recueillies. Résultats Des 3823 enfants dépistés, 414 (10.8%) avaient un œdème pulmonaire lésionnel et 165 (40%) ont été inclus dans l’étude (124 étaient sous ventilation mécanique conventionnelle, 27 sous ventilation à haute fréquence par oscillation et 14 sous ventilation non invasive). Dans le groupe sous ventilation conventionnelle, 43.5% étaient ventilés avec un mode contrôlé à pression, le volume courant moyen était de 8.3±3.3 ml/kg et l’utilisation de la PEP et FiO2 était hétérogène. Conclusions Cette étude démontre une hétérogénéité dans les stratégies de ventilation mécanique employées chez les enfants souffrant d’un œdème pulmonaire lésionnel. Celle-ci pourrait être en partie reliée à la robustesse des critères diagnostiques actuellement utilisés pour définir l’ALI/SDRA. Une évaluation rigoureuse de ces stratégies est nécessaire pour guider la standardisation des soins et optimiser l’issue de ces patients.