Pneumococcal empyema and complicated pneumonias: global trends in incidence, prevalence, and serotype epidemiology.

This review evaluates the serotype epidemiology of complicated pneumococcal pneumonia (CPP) during the period 1990-2012. PubMed and EMBASE were searched using the terms "empyema", "complicated pneumonia", "pleural infection", "necrotizing pneumonia", "pleural effusion", "parapneumonic effusion", "pneumatocele", or "lung abscess"; "pneumococcal" or "Streptococcus pneumoniae"; and "serotype" for studies on the epidemiology of complicated pneumonias published from January 1, 1990 to October 1, 2013. Studies with data on incidence and serotypes were included; reviews, case reports, and conference abstracts were excluded. Of 152 papers, 84 fitted the inclusion criteria. A few pneumococcal serotypes were predominant causes of CPP, particularly serotypes 1, 19A, 3, 14, and 7F. CPP was a more common manifestation of pneumococcal disease among older (>2 years old) than younger children. The data support increases in both reported incidence rates and proportions of CPP in children and adults during the period 1990-2012; specific increases varied by geographic region. The proportions of serotype 3 and, particularly in Asia, serotype 19A CPP have increased, whereas most studies show declines in serotype 14. Serotype 1 has been a predominant cause of CPP since 1990, while antibiotic resistance was infrequent among serotype 1 isolates. The reported incidence and proportions of CPP among pneumonia cases steadily increased from 1990 to 2012. Several factors might account for these increases, including enhanced disease detection due to a higher index of suspicion, more sophisticated diagnostic assays, and changes in the prevalence of serotypes with capacity to invade the pleural space that were not targeted by the 7-valent pneumococcal conjugate vaccine (PCV7).

Validation of a multiplex reverse transcriptase PCR ELISA for the detection of 19 respiratory tract pathogens.

INTRODUCTION: Since acute respiratory tract infections inflict a high burden of disease in children worldwide, a multiplex reverse transcription polymerase chain reaction combined with a microwell hybridization assay (m-RT-PCR-ELISA) to detect 19 different respiratory pathogens was developed and validated. METHODS: A total of 430 respiratory specimens were retrospectively tested in parallel by both the advanced 19-valent m-RT-PCR-ELISA as well as by culture or individual RT-PCR assays used in clinical routine. RESULTS: The mean (median) sensitivity of the m-RT-PCR-ELISA in the retrospective test was 93.3% (95.1%; range 83.3-100 %), and the mean (median) specificity was 99.8 and 100 % (range 98.6-100 %), respectively. The mean positive predictive value was 99.3 % (range 93.4-100 %) and the mean negative predictive value was 95.3 % (range 98.4-100 %). Feasibility and clinical value of the 19-valent method was prospectively shown on 16,231 incoming clinical specimens from patients between 0 and 16 years of age with acute respiratory tract infections admitted to pediatric hospitals or private practices from October 2003 to June 2010 in three regions in Germany (Kiel, Mainz, Freiburg; Freiburg to June 2007 only). At least one microorganism was detected in 10,765 of 16,231 (66.3 %) clinical specimens: 5,044 RV, 1,999 RSV, 1,286 AV, 944 EV, 737 seasonal IVA, 173 pandemic IVA H1N1-2009, 899 MPV, 518 CV, 383 PIV3, 268 PIV1, 259 Mpn, 205 IVB, 164 PIV2, 144 PIV4, 103 Bp, 29 Cpn and 29 Bpp, while reovirus and Lpn were not present in these specimens from a pediatric population. More than one organism could be detected in 13.4 % of the specimens. CONCLUSIONS: The m-RT-PCR-ELISA evaluated here improves the spectrum for diagnosing respiratory infections and is a feasible instrument for individual diagnostic and epidemiological studies.

Can the booster interval for the tick-borne encephalitis (TBE) vaccine 'FSME-IMMUN' be prolonged? - A systematic review.

Tick-borne encephalitis (TBE) vaccines are effective and well tolerated. However, their acceptance and use by the public in endemic areas are suboptimal. To some extent this is due to the complicated dosing schedule requiring frequent boosters at variable intervals that even change with age. Simplification of the dosing schedule has failed so far as it is debated if the persistence of TBE virus (TBEV) antibodies is the only relevant factor for protection or if immune memory plays a decisive role as well. The objective here is to present the available evidence to determine the need for boosters and their interval after a primary series of three doses of FSME-IMMUN. A systematic literature review was conducted with a focus on serology, particularly seropersistence, immune memory, effectiveness, and vaccine breakthroughs (VB) of FSME-IMMUN. While after a 3-dose primary series seropositivity persisted for more than 10 years in >90% of younger subjects, it dropped to 37.5% in those 60 years or older. In contrast, field effectiveness of FSME-IMMUN remains high in irregularly vaccinated subjects and thus does not correlate well with the percentage of subjects achieving an arbitrarily defined threshold of persisting antibodies. FSME-IMMUN booster doses led to increases in antibody responses within 7 days. VB are rare and remain poorly understood. VB did not increase, and vaccine effectiveness did not significantly decrease with time since completion of the primary vaccination series or with the time since administration of the last vaccine dose. For all these reasons, data identified from this systematic review suggest that seropersistence alone does not explain the high effectiveness of FSME-IMMUN irrespective of the time since the last vaccine dose was administered. Induction of immunological memory characterized by a rapid and sustained secondary immune response is proving to be an alternative mechanism of action for protection against TBE. In this context Switzerland and Finland have adopted a longer booster interval (i.e., 10 years) following the three-dose primary immunization schedule without any evidence of harm at a population level. Longer booster intervals will likely drive up vaccine uptake. There is a lack of data to base an interval recommendation beyond 10 years.

Seropersistence and booster response following vaccination with FSME-IMMUN in children, adolescents, and young adults.

BACKGROUND: Tick-borne encephalitis (TBE) is a viral disease that can have a severe clinical course and considerable long-term morbidity. As no curative treatment exists, vaccination is the primary means of prevention. Long-term antibody seropersistence 2-5 years after the 3-dose primary immunization and 3-10 years after first booster was evaluated, as well as booster responses in children, adolescents and young adults. METHODS: Subjects who participated in these phase 4 prospective, open-label follow-up studies received all vaccinations with FSME-IMMUN. After 3-dose primary immunization, subjects were followed for 2-5 years. Overall, 205 out of 358 subjects (57%) received the first booster and 179 of these subjects (87%) enrolled in a further 10-year follow-up. Antibody seropersistence was assessed annually. Subjects with a TBE antibody titer below a pre-specified cut-off at the yearly blood draw received a booster. Seropositivity rates and geometric mean fold rises (GMFRs) were assessed. RESULTS: In children who received their 3-dose primary immunization between 1 and 15 years of age, the seropositivity rate 5 years after the 3rd dose was 84.9% by NT and 72.0% by ELISA. One month post-first booster, all subjects were seropositive by NT and 98.5% by ELISA. Response to first booster by GMFR ranged from 3.7 to 11.4. At 5 years post-first booster, seropositivity was 99.4% by NT and 97.5% by ELISA, and at 10 years, was 90.3% by NT and 87.7% by ELISA. Although seropositivity rates differed between age groups, all subjects (100%) who received a second booster responded with a robust increase of TBEV antibodies. DISCUSSION: Long-lasting seropersistence of TBEV antibodies after the 3-dose primary immunization and first booster was demonstrated as well as a competent immune memory response in those who received a first or second booster at any time during the 15-year follow-up. Therefore, an extension of FSME-IMMUN booster interval up to 10 years after the 3-dose primary immunization seems warranted. ClinicalTrials.gov Identifier: NCT00894686.

Varicella vaccination in Europe: are we ready for a universal childhood programme?

Safe and effective vaccines against varicella zoster virus (VZV), the aetiological agent of varicella and shingles, have been available in Europe for the last 5-10 years. The USA has had a universal childhood vaccination policy since 1995 and this has resulted in a dramatic decrease in the incidence, morbidity and mortality related to varicella. The economic and medical burden of VZV has led to discussions regarding both the desirability and feasibility of a similar routine immunisation policy for all European children. This article examines the epidemiology of varicella in Europe and how the data emerging from the USA can be used to achieve adequate prevention of the disease. It looks into the current evidence of the health economic evaluation of universal varicella vaccination and explores the concerns surrounding such a policy, including the postulated impact on the incidence of zoster. In conclusion, the Society of Independent European Vaccination Experts (SIEVE) recommends that the immunisation of susceptible adolescents needs to be urgently implemented, in addition to the current recommendations targeting high-risk patients, their close contacts with a negative history of varicella and seronegative health-care workers. A universal policy, optimally incorporating a two-dose schedule, will be needed to finally reduce the burden of disease of varicella from a societal point of view. The SIEVE recommends the implementation of such a policy as soon as financially and practically possible.

Comparison of the BD Directigen Flu A+B Kit and the Abbott TestPack RSV with a multiplex RT-PCR ELISA for rapid detection of influenza viruses and respiratory syncytial virus.

The Directigen Flu A+B enzyme immunoassay and the Abbott TestPack RSV enzyme immunoassay were each compared with a multiplex RT-PCR ELISA by testing 635 nasopharyngeal aspirates collected from children aged < 16 years who had been hospitalised with acute respiratory tract infection during the epidemic season 2002-2003. In this study, the sensitivity of the Directigen Flu A+B assay was unacceptably low (29.3% and 10.0%, respectively) for the detection of influenza A and B viruses. The sensitivity of the Abbott TestPack RSV assay (77.4%) was acceptable and in agreement with the multiplex RT-PCR ELISA.

Fusarium infections in patients with hematologic malignancies.

Two cases of Fusarium infection in patients with refractory hematologic malignancies are reported. In one patient septicemia progressed to death in septic shock. Miconazole showed some effect in clearing the lesions. There is some evidence that mycotoxins are related with Fusarium infections since severe myositis occurred in our patient. The other patient had a T-cell lymphoma, undergoing allogeneic bone marrow transplantation. The course was also complicated by Fusarium infection of the skin. This patient died of multiorgan failure. Recent literature on Fusarium is reviewed.

A serologic study of organisms possibly associated with pertussis-like coughing.

OBJECTIVE: To assess the frequency of serologic evidence for an infection with microorganisms other than Bordetella pertussis in children with pertussis-like coughs. METHODS: The study was performed within a protective efficacy trial of an acellular pertussis vaccine. Children who coughed for >7 days and had no laboratory evidence of recent infection with B. pertussis were eligible for the present study. Antibodies to Mycoplasma, Chlamydia, respiratory syncytial virus and influenza viruses A and B were measured by complement fixation, and antibodies to adenovirus and parainfluenza viruses 1, 2 and 3 were measured by enzyme-linked immunosorbent assay (ELISA) in acute and convalescent serum samples. Significant titer rises (4-fold titer rise in complement fixation, 100% increase of units in ELISA) and concentrations of antibodies beyond age-specific reference values were regarded as indicative of recent infection. In some children IgM antibodies to Epstein-Barr virus and to cytomegalovirus were also measured by ELISA. RESULTS: A total of 149 of 1179 (12.6%) children had no laboratory evidence of B. pertussis infection. Serologic evidence for other infections were found in 56% (83 of 149). Adenovirus (33), parainfluenza viruses 1, 2 and 3 (18), Mycoplasma pneumoniae (15) and respiratory syncytial virus (14) were most common. Of this group 48% had been vaccinated against pertussis. CONCLUSION: We present data that a proportion of pertussis-like coughs in children may be caused by adenovirus, parainfluenza viruses, respiratory syncytial virus and Mycoplasma. The differential diagnosis of pertussis-like coughs by laboratory methods should include these infections, especially in vaccinated children.

Haemophilus influenzae type b disease: impact and effectiveness of diphtheria-tetanus toxoids-acellular pertussis (-inactivated poliovirus)/H. influenzae type b combination vaccines.

BACKGROUND: Since 1996 in Germany primary infant immunization against Haemophilus influenzae has been most commonly given in the form of diphtheria-tetanus toxoids-acellular pertussis/H. influenzae type b (DTaP/Hib) or diphtheria-tetanus toxoids-acellular pertussis (-inactivated poliovirus)/H. influenzae type b (DTaP-IPV/Hib) combination vaccines. These combination vaccines elicit lower anti-Hib antibody concentrations than the equivalent Hib conjugate administered as a separate injection, but the clinical relevance of this phenomenon is unknown. METHODS AND FINDINGS: To assess the impact of DTaP/Hib combination vaccines on the incidence of invasive Hib disease in Germany, two independent surveillance systems, one hospital- and one laboratory-based, were used during 1998 and 1999 for detection of cases. Vaccination histories of all cases detected were obtained by telephone contact with parents or health care providers. During the 2-year study period invasive H. influenzae disease in the <5-year age group continued to fall, with a mean annual incidence of 1.01/100 000 children. National vaccination coverage rates revealed that only 70% of children given DTaP/Hib or DTaP-IPV/Hib received the recommended three doses in their first year of life, but the overall effectiveness of these vaccines was high at 97.5% (95% confidence interval, 96.3 to 98.4) for those who had received at least one dose. In subjects who received the full 3-dose schedule, effectiveness was 98.8% (95% confidence interval, 98.2 to 99.3). CONCLUSION: Although it is well-documented that DTaP/Hib vaccines elicit lower anti-Hib titers than separate vaccines, such combinations are effective in reducing the incidence of invasive H. influenzae type b disease.

Evaluation of a multiplex reverse transcriptase PCR ELISA for the detection of nine respiratory tract pathogens.

BACKGROUND: A multiplex reverse transcription (RT) polymerase chain reaction combined with a microwell hybridization assay (m-RT-PCR-ELISA) was previously developed to detect nine different microorganisms: enterovirus (EV), influenza virus type A (IVA) and type B (IVB), respiratory syncytial virus (RSV), parainfluenzavirus type 1 (PIV1) and type 3 (PIV3), adenovirus (AV), Mycoplasma pneumoniae (Mpn), Chlamydia pneumoniae (Cpn) in a single test. These organisms do not usually colonize the respiratory tract of humans, but, if present, it may be assumed they are involved in respiratory disease. OBJECTIVES AND STUDY DESIGN: The m-RT-PCR-ELISA was tested on (i) culture supernatants of unknown contents, (ii) by determining the analytical sensitivity of 10-fold serial dilutions of culture supernatants and (iii) by determining clinical sensitivity in a retrospective study on 411 clinical specimens. The specimens were re-tested in parallel by m-RT-PCR-ELISA versus the gold standard culture and immunfluorescence, and versus individual RT-PCR. RESULTS: (i) The 9-valent m-RT-PCR-ELISA shows 83% to 100% concordant results on 103 culture supernatants containing different organisms. (ii) The analytical sensitivity was as follows: higher sensitivity of the 9-valent m-RT-PCR-ELISA in comparison to culture in the cases of PIV3, IVA and IVB (factor 10) and AV and EV (factor 100), and lower sensitivity in case of RSV and PIV1 (factor 10). (iii) The agreement with the gold standard in the kappa statistic was excellent for RSV (kappa = 0.937), IVA (kappa = 0.940), very good for PIV1 (kappa = 0.914), IVB (kappa = 0.907) and satisfactory for PIV3 (kappa = 0.410). For AV, EV and Mpn the m-RT-PCR-ELISA preliminary could be qualified as very good, based on the data derived on culture supernatants. Information about the validity for Cpn is limited. CONCLUSION: The m-RT-PCR-ELISA is a feasible, sensitive and specific method for detection of a broad spectrum of organisms. It is suitable for individual as well as epidemiological diagnosis.

Chirp optical coherence tomography of layered scattering media.

A new noninvasive technique that reveals cross sectional images of scattering media is presented. It is based on a continuous wave frequency modulated radar, but uses a tunable laser in the near infrared. As the full width at half maximum resolution of 16 µm is demonstrated with an external cavity laser, the chirp optical coherence tomography becomes an alternative to conventional short coherence tomography with the advantage of a simplified optical setup. The analysis of two-layer solid phantoms shows that the backscattered light gets stronger with decreasing anisotropic factor and increasing scattering coefficient, as predicted by Monte Carlo simulations. By introducing a two-phase chirp sequence, the combination of lateral resolved perfusion and depth resolved structure is shown. © 1998 Society of Photo-Optical Instrumentation Engineers.

Neuronal protection by intraischemic brain perfusion: an electron microscopy study in the rat.

Organ perfusion with bloodless solutions is an established clinical method for protecting the heart against ischemic damage. In our study, we evaluated the effects of intraischemic bloodless brain perfusion on postischemic ultrastructural neuronal changes in a model of severe incomplete forebrain ischemia produced by hemorrhagic hypotension combined with temporary carotid occlusion in the rat. Four groups of rats were compared. During an ischemic insult of 30 min, the brains of two groups were perfused via both external carotids with either a normosmolar normothermic magnesium-enriched perfusate (MgSO4, 30 mM; NaCl, 37 mM; mannitol, 180 mM; n = 10) or a normothermic normal saline solution (n = 9) at a rate of 6 ml/h. Two other groups (ischemia without perfusion, n = 8; no ischemia and no perfusion, n = 7) served as controls. After 30 min of ischemia, withdrawn blood for hemorrhagic hypotension was reinfused, the carotid arteries reopened, and the brains reperfused for 2 h. After perfusion-fixation, qualitative and quantitative evaluation of postischemic cell changes of hippocampal CA1 neurons was performed by electron microscopy. Brain perfusion with the magnesium-containing solution significantly protected neurons against ischemic cell changes and provided an ultrastructural pattern similar to that seen in the nonischemic control group. In contrast, brain perfusion with normal saline solution did not result in neuronal protection. We conclude that intraischemic intracarotid brain perfusion with magnesium-enriched perfusate protects hippocampal neurons significantly against ischemic cell changes in the early reperfusion period after transient severe forebrain ischemia.

Evoked otoacoustic emissions and pure tone threshold audiometry in patients receiving cisplatinum therapy.

Eight children and young adults with cancer were evaluated serially using pure tone audiometry as well as registration of click-evoked otoacoustic emissions (EOAE) 1 day prior to therapy as well as after various numbers of doses of cisplatinum. A reduction of EOAE-amplitudes following cisplatinum therapy was observed in all patients. This reduction tended to recover after the end of cisplatinum administration. Since EOAE are believed to result from cochlear bio-mechanical processes, the reduced emissions are interpreted as signs of cochlear dysfunction. We conclude, that EOAE testing may be a simple, non-invasive method that may detect early, transient functional impairment of hearing due to ototoxic agents such as cisplatinum, even in children. Further controlled trials are needed.

Serial measurements of transient evoked otoacoustic emissions (TEOAEs) in healthy newborns and in newborns with perinatal infection.

Detection of hearing impairment in early childhood is difficult. We serially recorded transient evoked otoacoustic emissions (TEOAEs) to search for signs of ototoxicity in term, healthy newborns and compared the results to a second group of term babies treated for perinatally acquired bacterial infection with ampicillin plus either cefotaxime or plus aminoglycoside. At initial evaluation, in the group of 45 healthy children born at term, well reproducible emissions were observed in all but two children. In each of these two, initially well reproducible TEOAEs were detected in one ear only. At the time of the second recording (mean at day 8.5) excellent emissions were seen in all ears of all children. Similarly, in the second group receiving ampicillin plus either cefotaxime or plus aminoglycoside, the height of emissions as well as TEOAE-reproducibility was equal or even increased at the time of the second evaluation in all 17 patients. In the following group of 59 patients, all receiving ampicillin plus aminoglycoside, again TEOAEs were equal or improved at the time of follow-up examinations. In all patients, a reduced general condition tended to be associated with less reproducible TEOAEs. We conclude that at conventional doses in low-risk infants, aminoglycosides are unlikely to cause ototoxicity and that in early childhood serial TEOAE-recording may be useful for evaluation of inner ear function.

Tonic cervical stimulation: does it influence eye position and eye movements in man?

In healthy subjects eye movements were analysed during body rotation, during trunk torsion either with the head passively held stationary in space or with the head voluntarily stabilized in space, and during voluntary head movements. Trapezoidal movements around the vertical axis were performed (+/- 40 degrees, plateau 10 s, duration of ramp 1 or 4 s). Moreover the influence of a tonic head deviation up to 40 degrees on optokinetic nystagmus and on vestibulo-ocular reflex during sinusoidal turning was examined. Eye movements were recorded by DC-electrooculography. Saccadic and slow components of eye movements and the shift of eye position during the plateau of the trapezoidal stimulus were analysed. For all modes of stimulation during the plateau no nystagmus occurred. At the end of the dynamic phase of the stimulus relatively frequent eye deviations--mostly in the direction of the head deviation--were observed, not only after turning the trunk with the head stabilized in space (cervical stimulation) but also after turning head and trunk together. The fact that such eye deviations are thus observed even in the absence of any tonic, especially cervical stimulus, supports the assumption that they cannot be attributed to a tonic stimulus but merely to an effect of the preceding phasic stimulus which outlasts them. Also amplitude and direction of eye shifts during the plateau do not depend on a tonic stimulus, but merely on the eye deviation reached at the end of the dynamic phase of stimulation. Optokinetic nystagmus and vestibulo-ocular reflex are not influenced by an additional tonic cervical stimulus.

Safety and efficacy of acellular pertussis vaccines: the Mainz study and other recent studies.

Following concerns about the safety and reactogenicity profile of diphtheria, tetanus and whole cell pertussis vaccines (DTwP), new and less reactogenic alternatives were developed over the last two decades. The new diphtheria, tetanus and acellular pertussis vaccines (DTaP) no longer consist of the whole bacterial cell but of either extracts or of a few highly purified components. While it soon became clear that DTaP vaccines are significantly less reactogenic than DTwP vaccines, their efficacy was disputed and remained unproven. First studies and epidemiological data from Japan suggested vaccine efficacy rates (VE) of about 80%; however, the first blinded clinical trial from Sweden documented a much lower VE. Worldwide, seven large DTaP efficacy trials have recently been completed. Our own efforts included a large safety trial with 22505 vaccinees and, nested in this setting, a prospective household contact study. Typical WHO-defined pertussis developed in 7 of 112 DTaP vaccinated children following household exposure as compared to 96 cases in 173 children not vaccinated against pertussis. Thus, vaccine efficacy was calculated to be 88.7% (95% CI 76.6 to 94.6). The median duration of spasmodic cough in the few children vaccinated with DTaP who did start coughing was 17 days as compared to 35 days in unvaccinated children. No waning of protection was observed. None of the confounding variables analyzed influenced study results in favour of DTaP. Following administration of more than 67000 DTaP doses, 153 serious adverse events were reported. Eight events were considered possibly related and five were considered related to the study vaccine. According to additional study results from the other trials it can be concluded that DTaP vaccines, like DTwP vaccines, are safe and effective. The choice between DTwP and DTaP should be based on acceptance of the reactogenicity profile, coverage rates achieved, costs and other factors in each individual country.

Epidemiology of pneumococcal disease in children in Germany.

UNLABELLED: Recently published and as yet unpublished data allow a reasonable estimate of the annual burden of pneumococcal disease in Germany. At least 277,000 episodes of otitis media and at least 2,000 episodes of sinusitis occur in children under the age of 5 y. Pneumococcal meningitis was found in 200 children under the age of 16 y; the estimate for all age groups ranges from 450 to 1100 cases. Of approximately 150,000 cases of ambulatory pneumococcal pneumonia, at least 63,000-105,000 patients are hospitalized each year. CONCLUSION: Further studies of pneumococcal epidemiology in Germany are needed, and continued surveillance will be necessary for a better understanding of the overall burden of pneumococcal disease in children as well as adults.

[Microwave volumetry of the extremities: a technical measuring alternative to the noninvasive venous occlusion test]. / Mikrowellen-Volumetrie der Extremitäten: eine messtechnische Alternative für den rückwirkungs-freien Venenverschlusstest.

Venous occlusion plethysmography is a well-established noninvasive procedure for the investigation of venous outflow disorders. Various different sensor systems are available for the purpose, e.g. photoplethysmography, strain-gauge plethysmography and impedance plethysmography. The technique of microwave volumetry described in this paper is based on the interaction of the electromagnetic fields within the loss medium, tissue, and uses an air-filled resonant cavity as a sensor. As in the case of a microwave oven, this is excited by a high-frequency generator, but involves the use of far less power. As the volume of the measured objects (foot, arm) increases, the losses in the resonator also increase and can be analysed in a computer. The results can be represented in the form of a classical venous occlusion curve.

Etomidate activates epileptic high frequency oscillations.

OBJECTIVE: The short acting anesthetic etomidate has been shown to provoke epileptic spikes and rarely seizures. Influence of etomidate on the occurrence of epileptic HFO (high frequency oscillations) however is unknown. An HFO inducing effect of etomidate would allow further validation of the substance as a provocation measure in presurgical evaluation as well as provide insights into the common mechanisms of HFO, spike and seizure generation. METHODS: We retrospectively analyzed EEG data from four patients who underwent etomidate activation during invasive video-EEG monitoring with subdural strip electrodes. Spikes were manually selected in raw data, HFO in band pass filtered data (80-250Hz). Rate and spatial distribution of HFO and spikes in three segments were compared: immediately after etomidate administration, as well as during slow wave sleep and while awake. RESULTS: Rates of HFO and spikes increased significantly after etomidate administration: Overall average rates of spikes were 9.7/min during sleep, 10/min while awake and 61.4/min after etomidate. Average HFO rates were 9.5/min during sleep, 8.3/min while awake and 24.4/min after etomidate (p<0.001, non-parametric ANOVA). Spatial distributions of HFO and spikes after administration of etomidate were consistent with the seizure onset zone (SOZ) and area of resection when available (SOZ: two patients; resection: one patient; no information: one patient). Except for spurious events, no additional HFO and spike foci were seen with activation. CONCLUSIONS: Etomidate administration activates spikes and HFO. Spatial distributions do not extend beyond electrodes showing spikes and HFO without Etomidate and seem consistent with the epileptic network. SIGNIFICANCE: Etomidate activation is a safe procedure to provoke not only epileptic spikes but also HFO, which were shown to have a high specificity for the SOZ.