Pediatric ambulatory pertussis epidemiology in France, recent updates.

OBJECTIVES: Following various changes in the vaccine strategy in 2013 and the mandatory vaccination in 2018, we aimed to analyze the vaccination status, age, and source of contamination of pertussis and parapertussis cases in outpatient surveillance. PATIENTS AND METHODS: Confirmed pertussis and parapertussis cases were enrolled by 35 pediatricians. RESULTS: From 2014 to 2022, 73 confirmed cases of pertussis (n = 65) and parapertussis (n = 8) were reported. For children below 6 years of age, the number of cases with a 2 + 1 schedule (n = 22) was higher than that of those with a 3 + 1 schedule (n = 7). The age of cases with a 3 + 1 or a 2 + 1 schedule was not significantly different (3.8y ± 1.4 vs 4.2y ± 1.5). The main source of contamination was either adults or adolescents. CONCLUSION: Vaccination status and source of contamination are crucial to study the impact of vaccination recommendations.

From the original SARS-CoV-2 strain to the Omicron variant: Predictors of COVID-19 in ambulatory symptomatic children.

OBJECTIVES: To determine the predictors of a positive SARS-CoV-2 test in a pediatric ambulatory setting. PATIENTS AND METHODS: We performed a cross-sectional prospective study (November 2020-February 2022) of 93 ambulatory settings in France. We included symptomatic children < 15 years old tested for SARS-CoV-2. For each period corresponding to the spread of the original strain and its variants (period 1: original strain; period 2: Alpha, period 3: Delta; period 4: Omicron), we used a multivariate analysis to estimate adjusted odds ratios (aORs) associated with COVID-19 among age, signs, symptoms or contact, and 95 % confidence intervals (95CIs). RESULTS: Of 5,336 children, 13.9 % (95CI 13.0-14.8) had a positive test. During the first three periods, the positivity rate ranged from 5.6 % (95CI 4.6-6.7) to 12.6 % (95CI 10.8-14.6). The main factors associated with a positive test were contact with an infected adult at home or outside the home (aOR 11.5 [95CI 4.9-26.9] to 38.9 [95CI 19.3-78.7]) or an infected household child (aOR 15.0 [95CI 4.8-47.1] to 28.4 [95CI 8.7-92.6]). By contrast, during period 4, aORs for these predictors were substantially lower (2.3 [95CI 1.1-4.5] to 5.5 [95CI 3.2-7.7]), but the positivity rate was 45.7 % (95CI 42.3-49.2). CONCLUSIONS: In pediatric ambulatory settings, before the Omicron period, the main predictor of a positive test was contact with an infected person. During the Omicron period, the odds of these predictors were substantially lower while the positivity rate was higher. An accurate diagnostic strategy should only rely on testing and not on age, signs, symptoms or contact.

Infovac-France survey in pediatric vaccinology: How does it compare with the literature?

BACKGROUND: Immunization is experienced as painful and may be responsible for needle fear and noncompliance. There are rare evidence-based methods to reduce pain and improve comfort during immunization. There are no French immunization guidelines summarizing the good practices, based on recent studies. This study focused on the methods used by physicians and how they compared with those validated by clinical trials. METHODS: An online questionnaire was sent to the practitioners from the Infovac network, and a PubMed bibliographic search was conducted. RESULTS: Almost 2000 doctors responded to this survey. Purging the needle was a habit in 77.9% of them and aspiration before injection in 21.1%. Only one-quarter of the responding doctors injected in the deltoid muscle between 15 and 24 months, and some injected in the buttocks at any age. Half of the physicians vaccinated infants in their parent's arms, children were seated with half of the pediatricians and only one-third of the general practitioners (GPs), and teenagers were seated when vaccinated by three-quarters of the doctors. Anesthetic creams were used by 46.6% of the physicians, mostly by pediatricians (61.9%), and for infants. Breastfeeding was suggested by three-quarters of the physicians for infants under 4 months of age, and sugared solutions were used by 55.5% of the pediatricians and 32.3% of the GPs. Half of the doctors used rocking and cuddling for babies under 24 months of age and toys between 11 and 24 months. CONCLUSION: Many methods are available to distract and improve comfort during immunization. Physicians should choose those they prefer, adjusting for the child's age. There should be French guidelines for immunization techniques, based to the latest clinical surveys, to help improve immunization practice.

Timeliness of routine immunization in non-preterm children less than 2 years old using electronic data capture in an ambulatory setting in France in the context of vaccine hesitancy.

OBJECTIVES: The vaccine schedule was changed in 2013 in France, which resulted in fewer vaccinations. However, to maintain disease protection, both vaccine timeliness and high coverage should be respected. In the context of growing vaccine hesitancy, we aimed to describe compliance with the immunization program according to the age recommended for each dose for non-preterm children less than 2 years old. METHODS: Between May 2013 and April 2016, we used automated electronic data capture of electronic medical records for non-preterm children less than 2 years old. Children were followed up by 92 randomly selected pediatricians from the French ambulatory pediatricians group. Delayed immunization was defined as more than 15 days after the recommended age for the primary series of diphtheria-tetanus-pertussis-polio-Haemophilus influenzae b-hepatitis B (DTaP-IPV-Hib±HB) and 13-valent pneumococcal vaccine (PCV13), 2 months for boosters, 1 month for measles-mumps-rubella (MMR)/meningococcal C conjugate (Men-C), and 6 months for the second dose of MMR. An association between delayed first dose and other doses delayed were described with odds ratios (ORs) and their 95% confidence intervals (CIs). RESULTS: Data for 22,097 children in France with 124,702 vaccinations were analyzed: 21.8%, 20.4%, and 30.7% of children had one or more delayed doses of DTaP-IPV-Hib±HB, PCV13, and MMR vaccines, respectively. For 47.6% of children, the single-dose Men-C vaccination was delayed. A delayed first dose of DTaP-IPV-Hib±HB, PCV13, and MMR was associated with a delayed second dose of the same vaccine (OR 7.5 [95% CI 6.6-8.6], 39.0 [34.1-44.8], and 23.5 [19.1-29.0], respectively) and with a third dose of DTaP-IPV-Hib±HB and PCV13 (14.7 [13.3-17.7] and 3.7 [3.1-4.5]). CONCLUSION: This large study shows that the proportion of children with delayed vaccination in France was globally high and substantial for Men-C and the first MMR vaccination. Risk of a delayed second and third dose was increased with a delayed first dose, which may reflect vaccine hesitancy.

Combination therapy with ciprofloxacin and third-generation cephalosporin versus third-generation cephalosporin monotherapy in Escherichia coli meningitis in infants: a multicentre propensity score-matched observational study.

OBJECTIVES: Escherichiacoli is the second cause of bacterial meningitis in neonates. Despite the use for 35 years of third-generation cephalosporins (3GCs), high morbidity and mortality rates with E. coli meningitis continue to occur. Because ciprofloxacin has good microbiologic activity against E. coli and good penetration in cerebrospinal fluid and brain, some authors have suggested adding ciprofloxacin to a 3GC regimen. The objective of this study was to assess combining 3GCs with ciprofloxacin versus 3GCs alone in a cohort of infants with E. coli meningitis. METHODS: We included all cases of E. coli meningitis diagnosed in infants <12 months of age that were prospectively collected through the French paediatric meningitis surveillance network between 2001 and 2016. The main outcome was the proportion of short-term neurologic complications with versus without ciprofloxacin. The analysis was conducted retrospectively by multivariable regression and propensity score (PS) analysis. RESULTS: Among the 367 infants enrolled, 201 (54.8%) of 367 had ciprofloxacin and 3GC cotreatment and 166 (45.2%) of 367 only a 3GC. Median age and weight were 15 days (range, 1-318 days) and 3.42 kg (range, 0.66-9.4 kg). A total of 86 (23.4%) of 367 infants presented neurologic complications (seizures, strokes, empyema, abscesses, hydrocephalus, arachnoiditis); 57 received ciprofloxacin cotreatment. Complications were associated with ciprofloxacin cotreatment on multivariable analysis (odds ratio (OR) = 1.9; 95% confidence interval (CI), 1.1-3.4) and PS analysis (OR = 1.9; 95% CI, 1.1-3.3). Mortality rate did not differ with and without ciprofloxacin: 22 (10.9%) of 201 versus 16 (9.6%) of 166 deaths (OR = 0.7; 95% CI, 0.3-1.6; PS analysis). CONCLUSIONS: Ciprofloxacin added to 3GCs at least offers no advantage for neurologic outcome and mortality in infants with E. coli meningitis.

Pharmacocinétique et pharmacodynamie des antibiotiques : est-ce différent en néonatologie ?

Pharmacokinetic and pharmacodynamics (PK/PD) data on antimicrobial agents enable physicians to optimize their use in clinical practice. Neonates exhibit a large inter-individual variability in antibiotic levels due to immaturity and maturational changes in the first weeks of life. This variability explains the large therapeutic margins needed to ensure an optimal efficacy of antibiotics. These pharmacokinetic characteristics have to be taken into account when treating neonatal sepsis, along with pharmacodynamics targets for each antibiotic and notably minimal inhibitory concentration for usual causes of neonatal bacterial infections (group B streptococcus and Escherichia coli). This paper presents PK/PD data of antimicrobial agents mainly used in neonatology (ß-lactamines and aminoglycosides) to help physicians to rationalize their use of antibiotics.

Effectiveness of endoscopic cricopharyngeal myotomy in adults with neurological disease: systematic review.

OBJECTIVE: To determine the effectiveness of endoscopic cricopharyngeal myotomy on upper oesophageal sphincter dysfunction in adults with upper oesophageal sphincter dysfunction and neurological disease. DATA SOURCES: Published and unpublished studies with a quasi-experimental design investigating endoscopic cricopharyngeal myotomy effects on upper oesophageal sphincter dysfunction in humans were considered eligible. Electronic databases, grey literature and reference lists of included studies were systematically searched. REVIEW METHODS: Data were extracted by two independent reviewers. Methodological quality was assessed independently using the PEDro scale and MINORS tool. RESULTS: Of 2938 records identified, 2 studies were eligible. Risk of bias assessment indicated areas of methodological concern in the literature. Statistical analysis was not possible because of the limited number of eligible studies. CONCLUSION: No determinations could be made regarding endoscopic cricopharyngeal myotomy effectiveness in the cohort of interest. Reliable and valid evidence on the following is required to support increasing clinical usage of endoscopic cricopharyngeal myotomy: optimal candidacy selection; standardised post-operative management protocol; complications; and endoscopic cricopharyngeal myotomy effects on aspiration of food and laryngeal penetration, mean upper oesophageal sphincter resting pressure and quality of life.

Outcomes of bacterial meningitis in children.

OBJECTIVE: Pediatricians are well aware of the immediate risks of bacterial meningitis in children. However, the long-term outcome of the disease has not been extensively studied. We aimed: (i) to evaluate the duration and quality of the long-term follow-up of children diagnosed with bacterial meningitis in a general pediatric department, (ii) to estimate the incidence of sequelae at the various stages of follow-up, and (iii) to compare our data with that of other studies. METHODS: We conducted a retrospective study and included 34 children (3 months-15 years) who had been hospitalized for bacterial meningitis in the pediatric department of a University Hospital between January 1st, 2001 and December 31st, 2013. RESULTS: Overall, 32% of patients presented with sequelae and 15% with seizures. Only one patient presented with hearing loss, but 23.5% of patients did not have any hearing test performed. Seven patients had a neuropsychological assessment performed and no severe neuropsychological sequela was observed in this group. The average follow-up duration increased during the study period (from 23 to 49months). The long-term follow-up modalities observed in other studies were highly variable. Assessing the incidence and severity of sequelae was therefore difficult. CONCLUSION: A standardized follow-up should be implemented by way of a national surveillance network of children presenting with bacterial meningitis.

[Implementation of meningococcal B vaccination (Bexsero®) in France: Physicians' perceptions and experiences of a few months after marketing approval]. / Introduction d'une vaccination contre le méningocoque B (Bexsero®) en France : perception et expérience des médecins quelques mois après l'autorisation de mise sur le marché.

BACKGROUND: In December 2013, the French public health authorities recommended the use of Bexsero® (meningococcus B vaccine) in areas with endemic risk and for patients at risk for invasive meningococcal B disease. In this context, InfoVac-France performed a national survey a few months after the implementation of the vaccine to evaluate physicians' perceptions and experiences with this new vaccine. METHODS: This survey was proposed by email in April 2014 to the InfoVac network. An initial email explained the purpose of this study and proposed an online questionnaire. RESULTS: Between April 29 and May 16, 2014, 1502 physicians answered online: 502 GPs (33%), 939 pediatricians (63%), and 61 other specialists (4%). In response, 91% of physicians would like to use this vaccine and 87% of pediatricians versus 50% of GPs knew that the vaccine was marketed. Physicians had been informed of the vaccine mostly via the InfoVac network (61%). The immunization schedules for all ages were slightly known by physicians (9% for GPs and 43% of pediatricians). This vaccination was still rarely proposed (18%) more often because it was not reimbursed to patients (62%). Although 39% of physicians were planning to propose the vaccine to their patients, 54% remained undecided. A total of 9% of pediatricians and 2% of GPs had already used this vaccination. CONCLUSION: This InfoVac-France survey shows that physicians would support the implementation of this vaccine, but questions persist as to its effectiveness, impact on carriage, and duration of protection.

[Impact of guidelines on ambulatory pediatric antibiotic prescriptions]. / Impact des recommandations sur la prescription en consultation de ville d'antibiotiques à l'enfant.

INTRODUCTION: The emergence of antibiotics resistance as a major public health threat has led, in France as in other countries, to the establishment of "antibiotics plans" based in part on practice guidelines. The objectives of this study were to determine the structure (number, causes, distribution of compounds) of antibiotic prescriptions by infectious diseases pediatricians (belonging to a pediatric infectious diseases research group), to check their compliance with guidelines and compare their prescriptions to other French pediatricians and general practitioners (GPs). PATIENTS AND METHODS: In a survey on acute otitis media (AOM), outpatient pediatricians reported prospectively from October 2013 to February 2014 all antibiotics prescribed and the reasons for these prescriptions. These results were compared with prescription data from a panel of other pediatricians and GPs in France (IMS Health panels). RESULTS: Between October 2013 and February 2014, 27 pediatricians from the Infectious Disease Pediatricians Group conducted 54,212 visits, 10.7 % of which resulted in antibiotic prescriptions, all diseases combined, compared to 12 % for other pediatricians and 21 % for GPs in the same period. AOM was the leading cause of prescriptions for infectious disease pediatricians and panel pediatricians, and GPs (respectively, 72.6 %, 33 %, and 25 %). Amoxicillin was the most frequently prescribed antibiotic (respectively, 71.7 %, 49.9 %, and 28.2 %). Cephalosporins were prescribed in 6.4 % of cases by infectious disease pediatricians versus 19 % for panel pediatricians and 19.9 % for GPs. CONCLUSION: The prescriptions of infectious disease pediatricians are in accordance with the French guidelines. The differences with the IMS data justify the need for continuous medical training and recommendations to promote these guidelines.

Liver iron overload assessment by MRI R2* relaxometry in highly transfused pediatric patients: an agreement and reproducibility study.

AIMS: Perform an agreement and reproducibility study of the estimation of iron overload in highly transfused pediatric patients comparing R2* relaxometry (R2*=1000/T2*) to the reference technique liver/muscle signal intensity ratio (SIR). PATIENTS AND METHODS: Ninety-two MRI were performed in 68 children who were mainly transfused for sickle cell disease, mean age 9.9 years old. The examination included six sequences for the SIR protocol and a single multiecho T2* sequence. R2* relaxometry was measured by two radiologists independently, either by a region of interest (ROI) in the right liver, or an outline of the whole liver. Hepatic iron load was determined by the Wood formula (Fe mg/g=R2*×0.0254+0.202). The validity of R2* relaxometry compared to SIR was evaluated by the coefficient of variation and the quadratic weighted Kappa value. RESULTS: The correlation between R2* relaxometry and SIR was very good with a Pearson coefficient of 0.89 and a coefficient of variation of 17.3%. The inter- and intraobserver reproducibility of the measurement of R2* relaxometry by ROI and whole liver mapping was excellent. However, we observed a common positive variation of one class between SIR and R2* relaxometry, with higher hepatic iron content values with SIR than with R2* relaxometry. CONCLUSION: Hepatic iron content can be rapidly and precisely estimated on MRI by multiecho gradient-echo sequences.

[Characteristics of group A streptococcal meningitis in children]. / Caractéristiques des méningites à streptocoque du groupe A de l'enfant.

Group A streptococcal (GAS) meningitis in children are rare. The aim of this study was to analyze the clinical, biological and outcome data on GAS meningitis recorded in the Bacterial Meningitis (BM) French Surveillance Network (GPIP/ACTIV). From 2001 through 2012, 4,564 children suffering from proven bacterial meningitis were recorded in the data base. Among them, 0.7 % were GAS infections. The median age was 5.6 years. A history of community acquired infection before the onset of GAS meningitis was frequent. Apart from the identification of the bacterial species, GAS meningitis were clinically and biologically indistinguishable from meningitis caused by other pathogens notably S. pneumoniae. Case fatality rate was 8 %.

[Use of group A streptococcal rapid diagnostic test in extra-pharyngeal infections]. / Utilisation des tests de diagnostic rapide du streptocoque du groupe A en dehors de l'angine.

The purpose of this study was to assess the performances of the group A streptococcus (GAS) rapid antigen diagnostic tests (RADTs) in extra-pharyngeal infections. Between October 2009 and June 2014, 368 patients (median age: 48 months) were enrolled. The pathologies involved were : 160 perineal infections (44 %), 69 blistering distal dactylitis (19 %), 55 cervical lymphadenitis (15 %), 31 crusty or bleeding rhinitis (8 %), and 53 other diseases (14 %). The sensitivity of GAS-RADT used was 96 % (95 % CI: 92-99 %), the specificity 81 % (95 % CI: 75- 86 %), the negative predictive value 97 % (CI 95 %: 93-99 %), and the positive predictive value 79 % (95 % CI: 73-85 %). Finally, positive and negative likelihood ratio were 5 (95 % CI: 4-7) and 0.05 (95 % CI: 0.02-0.11) respectively. The GAS-RADTs developed for pharyngitis have comparable performances in these settings and therefore can be used.

[Diagnostic of group A streptococcal blistering distal dactylitis]. / Diagnostic des tournioles à streptocoque du groupe A.

Blistering distal dactylitis is a distinct clinical entity, generally due to S. pyogenes, unfrequently reported. Characteristically, blistering distal dactylitis is described as a localized infection involving the distal phalanx of the digits, and it usually presents as a fluid-filled blister. Between October 2009 and June 2014, 69 children (median age: 60 months, extremes: 0,6-176) were enrolled. The sensitivity of GAS rapid antigen detection test was 97 % (CI 95 %: 83-100 %), the specificity was 76 % (CI 95 %: 60-89 %), the negative predictive value was 97 % (CI 95 %: 83-100 %), and the positive predictive value 76 % (CI 95 %: 60-89 %). All patients with a positive GAS rapid antigen test were treated with antibiotics (amoxicillin essentially) and cured without surgery.

[Group A streptococcal perineal infection in children]. / Infections périnéales à streptocoque du groupe A chez l'enfant.

Perineal diseases in children are usually caused by group A streptococcus (GAS). If the natural course of untreated cases is not known, it is well known that symptoms do not resolve spontaneously and can persist often for many months, until appropriate diagnosis and effective treatment are instituted. Furthermore, failures and recurrences after penicillin treatment are frequent. From 2009 to 2014, 165 perineal infections (median age: 48 months, extremes: 0.4-139) were enrolled by 15 pediatricians: 4 balanitis, 29 vulvo-vaginal diseases and 132 perianal infections. Painful defecation, anal fissures and macroscopic blood in stools were significantly more frequent in GAS perianal infections than negative GAS infections (p<0.01). The performance of GAS-rapid antigen test compared to the GAS culture was : sensitivity 97 % [CI 95 %: 89-100 %], specificity 76 % [CI 95 %: 66-84 %], negative predictive value 97 % [CI 95 %: 91-100 %], positive predictive value 71 % [CI 95 %: 60-80 %].

[Changes in bacterial meningitis in French children resulting from vaccination]. / Évolution des méningites bactériennes de l'enfant en France sous l'effet des vaccinations.

BACKGROUND: For the past 20 years, three vaccines against the three main bacterial species implicated in meningitis in children have been included in the French vaccine calendar: Haemophilus influenzae b in 1993, 7-valent pneumococcal conjugate vaccine (PCV7) in 2003 (replaced by 13-valent in 2010) and Neisseria meningitidis C in 2009. The French active surveillance network from the GPIP/ACTIV monitors the change in the epidemiological, clinical, and biological features of bacterial meningitis due to vaccine use. METHODS: Over a 12-year period, 233 pediatric wards working with 168 microbiology departments throughout France were asked to report all cases of bacterial meningitis. RESULTS: From January 2001 to December 2012, 4808 bacterial meningitis cases were reported. Between 2001 and 2012, the number of pneumococcal meningitis (PM) cases decreased by 23.4%, and by 32.2% for children less than 2 years old. During this period, the proportion of cases attributable to PCV7 and six additional PCV13 types decreased from 63.3% to 8.1% and 83.7% to 32.4%, respectively. In 2012, the main vaccine types (accounting for 25.8% of cases) were 7F (12.2%), 19A (6.8%), and 19F (6.8%), and the most frequent non-vaccine types were 12F (14.9%), 24F (14.9%), 15B/C (6.8%), 22F (6.8%), and 10A (5.4%). In 2012, the rate of strains with decreased susceptibility to cefotaxime/ceftriaxone (MIC>0.5 µg/mL) represented less than 3% of cases, with no identified resistant strain since 2010 (MIC>2 µg/mL). Between 2001 (n=67) and 2012 (n=9), the number of NmC meningitis cases decreased by 87%. CONCLUSION: With more than 4800 bacterial meningitis cases reported in 12 years, this nationwide survey provides essential information on the microbiological and clinical characteristics of bacterial meningitis (epidemiology or resistance data). These results could lead to changing antibiotic treatment of pneumococcal meningitis before the results of antibiotic susceptibility tests.

[Impact of corticosteroids in the immediate management of invasive meningococcal disease associated with hyperinvasive strains of the ST-11 clonal complex in children]. / Impact des corticoïdes dans la prise en charge immédiate des infections invasives à méningocoque liées aux souches hyper-invasives du complexe clonal ST-11 chez l'enfant.

OBJECTIVES: We used data from the Groupe de pathologie infectieuse pédiatrique and Association clinique et thérapeutique infantile du Val-de-Marne (GPIP/ACTIV) National Survey of Bacterial Meningitis in children and the National Reference Center for Meningococci (CNRM) microbiological data to assess the potential impact of corticosteroids on the immediate management of invasive meningococcal disease (IMD) associated with different genotypes, including highly pro-inflammatory strains of the ST-11 clonal complex (genotype ST-11). METHODS: From 2001 to 2009, 259 pediatric wards and 168 microbiology laboratories distributed throughout France prospectively included all under-18-year-old patients with IMD (meningitis or purpura fulminans). The strains were sent to the CNRM for genotyping. We linked the ACTIV clinical data of IMD cases, where information on corticosteroid therapy was available, to strains isolated by the CRNM. RESULTS: A total of 1981 IMD cases were identified during the 8-year study, 805 cases (712 [88.5%] bacterial meningitis and 93 [11.5%] purpura fulminans) had steroid treatment data (33.8% received corticosteroids). The genotype of the strains was available for 410 patients (24.4% related to genotype ST-11; 100 patients). For all cases and regardless of the corticosteroids, mortality was significantly associated with the genotype ST-11 (OR=2.39, 95% CI [1.29; 4.42], P=0.004). For all cases and regardless of the genotypes of the isolates, mortality was also significantly higher for children with than without corticosteroid therapy (12.7% versus 4.5%, P<0.001). However, this treatment had been prescribed more frequently in severe cases, including shock, PF, coma and/or mechanical ventilation. For children who did not receive corticosteroids, the mortality rate was significantly higher with genotype ST-11 compared to other genotypes (OR=4.68 [1.91, 11.46], P=0.001). This difference disappeared in children who received corticosteroids. CONCLUSION: This study indicates that in the absence of corticosteroids, higher mortality in invasive meningococcal disease is associated with the ST-11 clonal complex strains. This suggests a possible positive effect of corticosteroid therapy depending on the genotype of the strain involved.

Evidence for high-energy extraterrestrial neutrinos at the IceCube detector.

We report on results of an all-sky search for high-energy neutrino events interacting within the IceCube neutrino detector conducted between May 2010 and May 2012. The search follows up on the previous detection of two PeV neutrino events, with improved sensitivity and extended energy coverage down to about 30 TeV. Twenty-six additional events were observed, substantially more than expected from atmospheric backgrounds. Combined, both searches reject a purely atmospheric origin for the 28 events at the 4σ level. These 28 events, which include the highest energy neutrinos ever observed, have flavors, directions, and energies inconsistent with those expected from the atmospheric muon and neutrino backgrounds. These properties are, however, consistent with generic predictions for an additional component of extraterrestrial origin.

Measurement of atmospheric neutrino oscillations with IceCube.

We present the first statistically significant detection of neutrino oscillations in the high-energy regime (>20 GeV) from an analysis of IceCube Neutrino Observatory data collected in 2010 and 2011. This measurement is made possible by the low-energy threshold of the DeepCore detector (~20 GeV) and benefits from the use of the IceCube detector as a veto against cosmic-ray-induced muon background. The oscillation signal was detected within a low-energy muon neutrino sample (20-100 GeV) extracted from data collected by DeepCore. A high-energy muon neutrino sample (100 GeV-10 TeV) was extracted from IceCube data to constrain systematic uncertainties. The disappearance of low-energy upward-going muon neutrinos was observed, and the nonoscillation hypothesis is rejected with more than 5σ significance. In a two-neutrino flavor formalism, our data are best described by the atmospheric neutrino oscillation parameters |Δm(32)(2)|=(2.3(-0.5)(+0.6))×10(-3) eV(2) and sin(2)(2θ(23))>0.93, and maximum mixing is favored.