The impact of 10-valent pneumococcal vaccine introduction on invasive disease in Fiji.

BACKGROUND: In 2012, Fiji introduced the 10-valent pneumococcal conjugate vaccine (PCV10). We assessed the impact of PCV10 on invasive pneumococcal disease (IPD), probable bacterial or pneumococcal meningitis (PBPM), meningitis and sepsis 3-5 years post-introduction. METHODS: Laboratory-confirmed IPD and PBPM cases were extracted from national laboratory records. ICD-10-AM coded all-cause meningitis and sepsis cases were extracted from national hospitalisation records. Incidence rate ratios were used to compare outcomes pre/post-PCV10, stratified by age groups: 1-23m, 2-4y, 5-9y, 10-19y, 20-54y, ≥55y. To account for different detection and serotyping methods in the pre-and post-PCV10 period, a Bayesian inference model estimated serotype-specific changes in IPD, using pneumococcal carriage and surveillance data. FINDINGS: There were 423 IPD, 1,029 PBPM, 1,391 all-cause meningitis and 7,611 all-cause sepsis cases. Five years post-PCV10 introduction, IPD declined by 60% (95%CI: 37%, 76%) in children 1-23m months old, and in age groups 2-4y, 5-9y, 10-19y although confidence intervals spanned zero. PBPM declined by 36% (95%CI: 21%, 48%) among children 1-23 months old, and in all other age groups, although some confidence intervals spanned zero. Among children <5y of age, PCV10-type IPD declined by 83% (95%CI; 70%, 90%) and with no evidence of change in non-PCV10-type IPD (9%, 95%CI; -69, 43%). There was no change in all-cause meningitis or sepsis. Post-PCV10, the most common serotypes in vaccine age-eligible and non-age eligible people were serotypes 8 and 23B, and 3 and 7F, respectively. INTERPRETATIONS: Our study demonstrates the effectiveness of PCV10 against IPD in a country in the Asia-Pacific of which there is a paucity of data. FUNDING: This study was support by the Department of Foreign Affairs and Trade of the Australian Government and Fiji Health Sector Support Program (FHSSP). FHSSP is implemented by Abt JTA on behalf of the Australian Government.

Environmental and health impacts of February 14, 2014 radiation release from the nation's only deep geologic nuclear waste repository.

The environmental impact of the February 14, 2014 radiation release from the nation's only deep geologic nuclear waste repository, the Waste Isolation Pilot Plant (WIPP) was assessed using monitoring data from an independent monitoring program conducted by the Carlsbad Environmental Monitoring & Research Center (CEMRC). After almost 15 years of safe and efficient operations, the WIPP had one of its waste drums rupture underground resulting in the release of moderate levels of radioactivity into the underground air. A small amount of radioactivity also escaped to the surface through the ventilation system and was detected above ground. It was the first unambiguous release from the WIPP repository. The dominant radionuclides released were americium and plutonium, in a ratio that matches the content of the breached drum. The accelerated air monitoring campaign, which began following the accident, indicates that releases were low and localized, and no radiation-related health effects among local workers or the public would be expected. The highest activity detected was 115.2 µBq/m(3) for (241)Am and 10.2 µBq/m(3) for (239+240)Pu at a sampling station located 91 m away from the underground air exhaust point and 81.4 µBq/m(3) of (241)Am and 5.8 µBq/m(3) of (239+240)Pu at a monitoring station located approximately one kilometer northwest of the WIPP facility. CEMRC's recent monitoring data show that the concentration levels of these radionuclides have returned to normal background levels and in many instances, are not even detectable, demonstrating no long-term environmental impacts of the recent radiation release event at the WIPP. This article presents an evaluation of almost one year of environmental monitoring data that informed the public that the levels of radiation that got out to the environment were very low and did not, and will not harm anyone or have any long-term environmental consequence. In terms of radiological risk at or in the vicinity of the WIPP site, the increased risk from the WIPP releases is exceedingly small, approaching zero.

Clinical and microbiological characteristics of Eggerthella lenta bacteremia.

Eggerthella lenta is an emerging pathogen that has been underrecognized due to historical difficulties with phenotypic identification. Until now, its pathogenicity, antimicrobial susceptibility profile, and optimal treatment have been poorly characterized. In this article, we report the largest cohort of patients with E. lenta bacteremia to date and describe in detail their clinical features, microbiologic characteristics, treatment, and outcomes. We identified 33 patients; the median age was 68 years, and there was no gender predominance. Twenty-seven patients (82%) had serious intra-abdominal pathology, often requiring a medical procedure. Of those who received antibiotics (28/33, 85%), the median duration of treatment was 21.5 days. Mortality from all causes was 6% at 7 days, 12% at 30 days, and 33% at 1 year. Of 26 isolates available for further testing, all were identified as E. lenta by both commercially available matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) systems, and none were found to harbor a vanA or vanB gene. Of 23 isolates which underwent susceptibility testing, all were susceptible to amoxicillin-clavulanate, cefoxitin, metronidazole, piperacillin-tazobactam, ertapenem, and meropenem, 91% were susceptible to clindamycin, 74% were susceptible to moxifloxacin, and 39% were susceptible to penicillin.

Radiation release at the nation's only operating deep geological repository--an independent monitoring perspective.

Recent incidents at the nation's only operating deep geologic nuclear waste repository, the Waste Isolation Pilot Plant (WIPP), resulted in the release of americium and plutonium from one or more defense-related transuranic (TRU) waste containers into the environment. WIPP is a U.S. Department of Energy mined geologic repository that has been in operation since March, 1999. Over 85,000 m3 of waste in various vented payload containers have been emplaced in the repository. The primary radionuclides within the disposed waste are 239+240Pu and 241Am, which account for more than 99% of the total TRU radioactivity disposed and scheduled for disposal in the repository. For the first time in its 15 years of operation, there was an airborne radiation release from the WIPP at approximately 11:30 PM Mountain Standard Time (MST) on Friday, February 14, 2014. The radiation release was likely caused by a chemical reaction inside a TRU waste drum that contained nitrate salts and organic sorbent materials. In a recent news release, DOE announced that photos taken of the waste underground showed evidence of heat and gas pressure resulting in a deformed lid, in material expelled through that deformation, and in melted plastic and rubber and polyethylene in the vicinity of that drum. Recent entries into underground Panel 7 have confirmed that at least one waste drum containing a nitrate salt bearing waste stream from Los Alamos National Laboratory was breached underground and was the most likely source of the release. Further investigation is underway to determine if other containers contributed to the release. Air monitoring across the WIPP site intensified following the first reports of radiation detection underground to ascertain whether or not there were releases to the ground surface. Independent analytical results of air filters from sampling stations on and near the WIPP facility have been released by us at the Carlsbad Environmental Monitoring & Research Center and confirmed trace amounts of 241Am and 239+240Pu, at ratios reflecting the suspect waste stream. The highest activity detected offsite was 115.2 µBq/m3 for 241Am and 10.2 µBq/m3 for 239+240 Pu. These concentrations in air were very small, localized, and below any level of public health or environmental concern.

An overview of Fukushima radionuclides measured in the northern hemisphere.

The Great East Japan Earthquake and tsunami on March 11, 2011 resulted in the tragic accident at the Fukushima Nuclear Power Plant (NPP) and subsequently uncontrolled release of radioactive contaminants into the atmosphere. This review article attempts to compile and interpret data collected by various national and international monitoring networks in response to the Fukushima releases across the northern hemisphere. The majority of the releases occurred during the period March 12-22 with a maximum release phase from March 14-17, 2011. The radioactivity released was dominated by volatile fission products including isotopes of the noble gases (xenon and krypton), iodine, cesium, and tellurium. The radioactive gases and particles released in the accident were dispersed over the middle latitudes of the entire northern hemisphere and for the first time also measured in the southern Hemisphere. Isotopes of iodine and cesium were detected in air, water, milk and food samples collected across the entire northern hemisphere. Elevated levels of fission products were detected from March to May 2011 at many locations over the northern hemisphere. This article focuses on the most prevalent cesium and iodine isotopes, but other secondary isotopes are also discussed. Spatial and temporal patterns and differences are contrasted. The activity ratios of (131)I/(137)Cs and (134)Cs/(137)Cs measured at several locations are evaluated to gain an insight into the fuel burn-up, the inventory of radionuclides in the reactor and the isotopic signature of the accident. It is important to note that all of the radiation levels detected outside of Japan have been very low and are well below any level of public and environmental hazard.

Severe thrombocytopenia and patterns of bleeding in neonates: results from a prospective observational study and implications for use of platelet transfusions.

OBJECTIVE: To describe patterns of clinical bleeding in neonates with severe thrombocytopenia (ST and platelet count <60 × 10(9) L(-1)), and to investigate the factors related to bleeding. STUDY DESIGN: Seven tertiary-level neonatal units enrolled neonates (n = 169) with ST. Data were collected prospectively on all clinically apparent haemorrhages. Relationships between bleeding, platelet count and baseline characteristics were explored through regression analysis. RESULTS: Bleeding was recorded in most neonates with ST (138/169; 82%), including 123 neonates with minor bleeding and 15 neonates with major bleeding. The most common sites of minor bleeding were from the renal tract (haematuria 40%), endotracheal tube (21%), nasogastric tube (10%) and skin (15%). Gestational age <34 weeks, development of ST within 10 days of birth and necrotizing enterocolitis were the strongest predictors for an increased number of bleeding events. For neonates with ST, a lower platelet count was not a strong predictor of increased bleeding. CONCLUSIONS: The majority of neonates with ST bleed, although most episodes are minor. These findings establish the importance of clinical factors for bleeding risk, rather than minimum platelet count. Further studies should assess the clinical significance of different types of minor bleed for neonatal outcomes, the predictive value of minor bleeding for major bleeding and the role of platelet transfusions in preventing bleeding.

Plutonium in the WIPP environment: its detection, distribution and behavior.

The Waste Isolation Pilot Plant (WIPP) is the only operating deep underground geologic nuclear repository in the United States. It is located in southeastern New Mexico, approximately 655 m (2150 ft) below the surface of the Earth in a bedded Permian evaporite salt formation. This mined geologic repository is designed for the safe disposal of transuranic (TRU) wastes generated from the US defense program. Aerosol and soil samples have been collected near the WIPP site to investigate the sources of plutonium in the WIPP environment since the late 1990s, well before WIPP received its first shipment. Activities of (238)Pu, (239+240)Pu and (241)Am were determined by alpha spectrometry following a series of chemical separations. The concentrations of Al and U were determined in a separate set of samples by inductively coupled plasma mass spectrometry. The annual airborne concentrations of (239+240)Pu during the period from 1998 to 2010 show no systematic interannual variations. However, monthly (239+240)Pu particulate concentrations show a typical seasonal variation with a maximum in spring, the time when strong and gusty winds frequently give rise to blowing dust. Resuspension of soil particles containing weapons fallout is considered to be the predominant source of plutonium in the WIPP area. Further, this work characterizes the source, temporal variation and its distribution with depth in a soil profile to evaluate the importance of transport mechanisms affecting the fate of these radionuclides in the WIPP environment. The mean (137)Cs/(239+240)Pu, (241)Am/(239+240)Pu activity ratio and (240)Pu/(239)Pu atom ratio observed in the WIPP samples are consistent with the source being largely global fallout. There is no evidence of any release from the WIPP contributing to radionuclide concentrations in the environment.

Radioactive fallout in the United States due to the Fukushima nuclear plant accident.

The release of radioactivity into the atmosphere from the damaged Fukushima Daiichi nuclear power plant started on March 12th, 2011. Among the various radionuclides released, iodine -131 ((131)I) and cesium isotopes ((137)Cs and (134)Cs) were transported across the Pacific Ocean and reached the United States on 17-18 March 2011. Consequently, an elevated level of fission products (131)I, (132)I, (132)Te, (134)Cs and (137)Cs were detected in air, water, and milk samples collected across the United States between March 17 and April 4, 2011. The continuous monitoring of activities over a period of 25 days and spatial variations across more than 100 sampling locations in the United States made it possible to characterize the contaminated air masses. For the entire period, the highest detected activity values ranged from less than 1 m Bq m(-3) to 31 m Bq m(-3) for the particulate (131)I, and up to 96 m Bq m(-3) for the gaseous (131)I fraction.

The EASTR Study: indications for transfusion and estimates of transfusion recipient numbers in hospitals supplied by the National Blood Service.

This study provides data on National Blood Service (NBS) red blood cell (RBC, n = 9142), platelet (PLT, n = 4232) and fresh frozen plasma (FFP, n = 3584) recipients independently sampled by monthly quota from 29 representative hospitals over 12 months in 2001-2002. Hospitals were stratified by size according to total yearly RBC issues. Transfusion indications were chosen from diagnostic and procedural codes, and recipients grouped into Epidemiology and Survival of Transfusion Recipients Case-mix Groups (E-CMGs). The main E-CMGs were digestive [19% of RBC recipients; including 5% gastrointestinal (GI) bleeds and 3% colorectal surgery], musculoskeletal (15%; 12% hip and knee replacement), haematology (13%) and obstetrics and gynaecology (10%). Renal failure, fractured neck of femur, cardiac artery by-pass grafting (CABG) and paediatrics, each accounted for 3-4% recipients. FFP recipients: the main E-CMGs were digestive (21% of FFP recipients; including 7% GI bleeds and 3% colorectal surgery), hepatobiliary (15%; 7% liver disease and 2% liver transplant), cardiac (12%) and paediatrics (9%) The renal, paediatrics, vascular and haematology E-CMGs each had 6-7% of recipients. PLT recipients: the main E-CMGs were haematology (27% of PLT recipients; including 9% lymphoma and 8% acute leukaemia), cardiac (17%), paediatrics (13%), hepatobiliary (10%) and digestive (9%). Back-weighting gave national estimates of 433 000 RBC, 57 500 FFP and 41 500 PLT recipients/year in England and North Wales, median age 69, 64 and 59 years, respectively. Digestive and hepatobiliary indications emerged as the top reason for transfusion in RBC and FFP recipients, and was also a frequent indication in PLT recipients.

The EASTR study: a new approach to determine the reasons for transfusion in epidemiological studies.

Previous studies of blood use have used different methods to obtain and classify transfusion indications. Before undertaking a national study of transfusion recipients, a pilot study was performed over 2 months at two teaching and two district general hospitals to match information from hospital transfusion laboratories with clinical coding data from the hospital's Patients Administration System to determine the indication for transfusion in 2468 recipients. Data analysis revealed major limitations in the conventional use of primary diagnostic International Statistical Classification of Disease and Related Health Problems 10th Revision (ICD-10) or procedure Office of Population, Censuses and Surveys - Classification of Surgical Operations and Procedures - 4th Revision (OPCS-4) codes alone in allocating transfusion indications. A novel algorithm was developed, using both types of code, to select the probable indication for transfusion for each patient. A primary OPCS-4 code was selected for recipients transfused in relation to surgery (43%) and either the primary (36%) or the secondary (12%) ICD-10 code was chosen for recipients transfused for medical reasons. The remaining patients were unclassified. Selected codes were then collated into Epidemiology and Survival of Transfusion Recipients (EASTR) casemix groups (E-CMGs). The most frequent E-CMGs were haematology (15% of recipients), musculoskeletal (14%), digestive system (12%) and cardiac (10%). The haematology E-CMG includes patients with malignant and non-malignant blood disorders and recipients transfused for anaemia where no cause was listed. Recipients undergoing hip and knee replacement and coronary artery bypass grafting are within the musculoskeletal and cardiac E-CMGs. The digestive E-CMG includes recipients transfused for gastrointestinal (GI) bleeds and those undergoing GI surgery. This methodology provides a more useful means of establishing the probable indication for transfusion and arranging recipients into clinically relevant groups.

Improved detection of vanB2-containing enterococcus faecium with vancomycin susceptibility by Etest using oxgall supplementation.

We have isolated a number of vanB-containing Enterococcus faecium isolates on bile esculin screening agar containing 6 mg/liter vancomycin, which on subsequent susceptibility testing using Etest have repeatedly demonstrated vancomycin MICs of

High rates of fecal carriage of nonenterococcal vanB in both children and adults.

We examined the rate of fecal carriage of vanB in the absence of cultivable vancomycin-resistant enterococci in three distinct populations (children, community adults, and hemodialysis patients). Nonenterococcal vanB carriage was similarly high in hemodialysis patients (45%) and community adults (63%; P = 0.066) and significantly more common among community adults than children (27%; P = 0.001).

Regional hemodynamic effects of neutral endopeptidase inhibition and angiotensin (AT(1)) receptor antagonism alone or in combination in conscious spontaneously hypertensive rats.

We tested the hypothesis that angiotensin (AT(1)) receptor antagonism (with losartan) would enhance the cardiovascular actions of neutral endopeptidase (NEP) inhibition [with candoxatrilat or (2S)-2-{[1-({[(1S)-1-carboxy-2-(5-phenyl-1,3-oxazol-2-yl)ethyl]amino}carbonyl)cyclopentyl]methyl}-4-methoxybutanoic acid (UK-489,329)] in conscious spontaneously hypertensive rats (SHR). Four-day continuous intravenous infusion of candoxatrilat (1.9 microg kg(-1) min(-1)) or UK-489,329 (0.15 microg kg(-1) min(-1)) had no significant cardiovascular effects, whereas candoxatrilat (6.4 microg kg(-1) min(-1)) had a modest antihypertensive effect (-10.9 mm Hg on day 4) but no significant sustained effects on regional hemodynamics. Losartan caused a fall in blood pressure (maximum -29.2 mm Hg on day 4) that was associated with renal, mesenteric, and, to a lesser extent, hindquarters vasodilatation. The combination of losartan with either dose of candoxatrilat had no greater antihypertensive or vasodilator effects than losartan alone, with the exception of the increase in renal vascular conductance, which was greater with the combination of the drugs than with either drug alone (significant only in the lower dose study). Losartan combined with UK-489,329 showed a greater antihypertensive effect than losartan alone (-14.6 mm Hg greater on day 4), although the effects of the combination were not significantly greater than the sum of the effects of both agents administered separately. However, losartan combined with UK-489,329 caused increases in renal and hindquarters vascular conductance that were significantly greater with the combination than with either agent given alone. Thus, in conscious SHR, the renin-angiotensin system may act to oppose a vasodilator action of NEP inhibition, particularly in the renal vascular bed.

Molecular characterization of vanB elements in naturally occurring gut anaerobes.

Previously, we reported the isolation of 10 vancomycin-resistant gram-positive anaerobic bacilli carrying the vanB ligase gene from nine hemodialysis patients (S. A. Ballard et al., Antimicrob. Agents Chemother. 49:77-81, 2005; T. P. Stinear et al., Lancet 357:855-856, 2001). In the present study, the molecular and evolutionary relationship of the vanB resistance element within these 10 anaerobes and two vancomycin-resistant Enterococcus faecium strains were examined. PCR analysis and nucleotide sequencing demonstrated that all 12 isolates carried the vanB operon associated with an element identical to Tn1549 and Tn5382 of Enterococcus. Restriction fragment length polymorphism analysis of the vanB operon in these isolates revealed two distinct patterns, and sequencing showed that minor base differences existed. PCR amplification of the joint region of a circular intermediate was demonstrated in nine of these organisms, a finding indicative of an ability to excise and circularize, an intermediate step in transposition and conjugative transfer. Southern hybridization with a vanB-vanX(B) probe suggests that there is one insert of the transposon in all isolates. Sequence analysis of the integration site revealed distinct sequences: the Tn1549/5382 element within E. faecium was inserted within the host chromosome, whereas nucleotide sequences surrounding the Tn1549/5382 element in the 10 anaerobes showed no significant homology to sequences in the GenBank database. We demonstrate considerable similarity between the Tn1549/5382 element identified in 10 anaerobe isolates with that found in enterococci. The homology and potential to transpose suggest a recent horizontal transfer event may have occurred. However, the original direction of transposition and the mechanism involved remains unknown.

Hemodynamic effects of phosphodiesterase 5 and angiotensin-converting enzyme inhibition alone or in combination in conscious SHR.

The regional hemodynamic responses to continuous 4-day infusion of UK-357,903 [1-ethyl-4-{3-[3-ethyl-6,7-dihydro-7-oxo-2-(2-pyridylmethyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl]-2-(2-methoxyethoxy)-5-pyridylsulphonyl}piperazine] (266 microg kg(-1) h(-1)) alone and in combination with a low dose of enalapril (10 microg kg(-1) h(-1)) were measured in conscious spontaneously hypertensive rats to test the hypothesis that the renin-angiotensin system may influence the cardiovascular consequences of inhibition of phosphodiesterase 5 (PDE5) by UK-357,903 or vice versa. UK-357,903 alone caused a fall in mean blood pressure (-12.1 mm Hg) associated with vasodilatation in the mesenteric and hindquarters vascular beds. The only way in which the effects of enalapril given alone differed significantly from those of the vehicle was in causing mesenteric vasodilatation, which developed over the 4 days of infusion. UK-357,903 given in combination with enalapril caused hypotension (-17.8 mm Hg) and vasodilatation in the renal, mesenteric, and hindquarter vascular beds. There was evidence of a significant interaction between the effects of the two compounds on renal Doppler shift and vascular conductance with the combined action of the two compounds being greater than the sum of their individual effects. However, although there was a trend for the combination to have greater effects than either of the individual agents on blood pressure and mesenteric vascular conductance, there was no statistical evidence of an interaction. The results indicate that inhibition of the renin-angiotensin system uncovers additional renal vasodilator effects of UK-357,903, and/or inhibition of PDE5 enhances the renal vasodilator effects of angiotensin-converting enzyme inhibition.

Comparison of three PCR primer sets for identification of vanB gene carriage in feces and correlation with carriage of vancomycin-resistant enterococci: interference by vanB-containing anaerobic bacilli.

We assessed the sensitivities and specificities of three previously described PCR primers on enrichment broth cultures of feces for the accurate detection of fecal carriage of vancomycin-resistant enterococci (VRE). In addition, we investigated specimens that were vanB PCR positive but VRE culture negative for the presence of other vanB-containing pathogens. Feces from 59 patients (12 patients carrying vanB Enterococcus faecium strains and 47 patients negative for VRE carriage) were cultured for 36 h in aerobic brain heart infusion (BHI) broth, anaerobic BHI (AnO(2)BHI) broth, or aerobic Enterococcosel (EC) broth. DNA was extracted from the cultures and tested for the presence of vanB by using the PCR primers of Dutka-Malen et al. (S. Dutka-Malen, S. Evers, and P. Courvalin, J. Clin. Microbiol. 33:24-27, 1995), Bell et al. (J. M. Bell, J. C. Paton, and J. Turnidge, J. Clin. Microbiol. 36:2187-2190, 1998), and Stinear et al. (T. P. Stinear, D. C. Olden, P. D. R. Johnson, J. K. Davies, and M. L. Grayson, Lancet 357:855-856, 2001). The sensitivity (specificity) of PCR compared with the results of culture on BHI, AnO(2)BHI, and EC broths were 67% (96%), 50% (94%), and 17% (100%), respectively, with the primers of Dutka-Malen et al.; 92% (60%), 92% (45%), and 92% (83%), respectively, with the primers of Bell et al.; and 92% (49%), 92% (43%), and 100% (51%) respectively, with the primers of Stinear et al. The primers of both Bell et al. and Stinear et al. were significantly more sensitive than those of Dutka-Malen et al. in EC broth (P = 0.001 and P < 0.001, respectively). The poor specificities for all primer pairs were due in part to the isolation and identification of six anaerobic gram-positive bacilli, Clostridium hathewayi (n = 3), a Clostridium innocuum-like organism (n = 1), Clostridium bolteae (n = 1), and Ruminococcus lactaris-like (n = 1), from five fecal specimens that were vanB positive but VRE culture negative. All six organisms were demonstrated to contain a vanB gene identical to that of VRE. VanB-containing bowel anaerobes may result in false-positive interpretation of PCR-positive fecal enrichment cultures as VRE, regardless of the primers and protocols used.