Changing demographics and immunity to vaccine preventable diseases in people with HIV in Ireland.

BACKGROUND: HIV infection is associated with an increased risk of morbidity and mortality from vaccine preventable infections. This research describes, in the context of changing patient demographics, the seroprevalence of vaccine preventable viral infections among attendees of the largest centre for HIV positive patients in Ireland. METHODS: Baseline serum IgG results for measles, mumps, rubella, varicella zoster virus (VZV) & hepatitis A, as well as hepatitis B sAg, cAb and sAb results, were retrieved for 2534 clinic attendees attending in 2018. Results were available for between 990 and 2363 attendees (39-93%), depending on the test, and were compared with 2013 clinic data. RESULTS: There was a 35% increase in attendees in 2018 when compared to 2013. The largest increase was in attendees of South American origin. In 2018, males accounted for 73% of the entire cohort and the HIV acquisition risk for 48% of attendees was MSM. 47% of attendees were originally from Ireland. Among those tested, 33% were susceptible to at least one component of the MMR vaccine. 5% were VZV non-immune (significantly associated with younger age and the acquisition risk status of injection drug use). 21% were hepatitis A non-immune (significantly associated with younger age and being of European or South American origin). 32% were hepatitis B cAb seropositive (significantly associated with older age, injection drug use status and being originally from Africa). 3% demonstrated hepatitis B sAg positivity. 64% had hepatitis B sAb ≥ 10mIU. CONCLUSION: In a cohort of attendees to an HIV clinic in a large urban setting, the susceptibility to several common vaccine preventable viral infections, in particular MMR and hepatitis A and B, was high. These results highlight the importance of proactive screening and immunisation to help protect this high risk patient group against vaccine preventable diseases.

Tick-borne Encephalitis Identified in Ireland: Diagnosis and Outcome.

Presentation Tick borne encephalitis (TBE) is not endemic in Ireland and diagnostic tests are seldom requested. We describe the first notified case in Ireland. A 50-year-old female returned from Lithuania and presented with fever and new neurologic signs. Diagnosis TBE was diagnosed by detection of TBE virus specific antibodies in serum and cerebrospinal fluid (CSF). Treatment The patient was managed with observation and supportive care consisting of intravenous fluids and analgesia. Discussion The case highlights the importance of awareness of TBE among physicians and travellers to guide appropriate testing and vaccination. TBE is being recognised in non-endemic countries posing an emerging risk to public health.

A Comparison of the Performance of SARS-CoV-2 Antibody Assays in Healthcare Workers with COVID-19.

Aims Since its emergence, significant interest surrounds the use of SARS-CoV-2 serological tests as an alternative or as an adjunct to molecular testing. However, given the speed of this pandemic, paralleled with the pressure to develop and provide serological tests in an expediated manner, not every assay has undergone the rigorous evaluation that is usually associated with medical diagnostic assays. We aimed to examine the performance of several commercially available SARS-CoV-2 IgG antibody assays among participants with confirmed COVID-19 disease and negative controls. Methods Serum taken between day 17 and day 40 post onset of symptoms from 41 healthcare workers with RT-PCR confirmed COVID-19 disease, and pre-pandemic serum from 20 negative controls, were tested for the presence of SARS-CoV-2 IgG using 7 different assays including point-of-care (POC) and laboratory-based assays. Results Assay performance varied. The lab-based Abbott diagnostics SARS-CoV-2 IgG assay proved to be the assay with the best positive and negative predictive value, and overall accuracy. The POC Nal von Minden GmbH and Biozek assays also performed well. Conclusion Our research demonstrates the variations in performance of several commercially available SARS-CoV-2 antibody assays. These findings identify the limitations of some serological tests for SARS-CoV-2. This information will help inform test selection and may have particular relevance to providers operating beyond accredited laboratories.

Antimicrobial resistance and molecular epidemiology using whole-genome sequencing of Neisseria gonorrhoeae in Ireland, 2014-2016: focus on extended-spectrum cephalosporins and azithromycin.

High-level resistance and treatment failures with ceftriaxone and azithromycin, the first-line agents for gonorrhoea treatment are reported and antimicrobial-resistant Neisseria gonorrhoeae is an urgent public health threat. Our aims were to determine antimicrobial resistance rates, resistance determinants and phylogeny of N. gonorrhoeae in Ireland, 2014-2016. Overall, 609 isolates from four University Hospitals were tested for susceptibility to extended-spectrum cephalosporins (ESCs) and azithromycin by the MIC Test Strips. Forty-three isolates were whole-genome sequenced based on elevated MICs. The resistance rate to ceftriaxone, cefixime, cefotaxime and azithromycin was 0, 1, 2.1 and 19%, respectively. Seven high-level azithromycin-resistant (HLAzi-R) isolates were identified, all susceptible to ceftriaxone. Mosaic penA alleles XXXIV, X and non-mosaic XIII, and G120K plus A121N/D/G (PorB1b), H105Y (MtrR) and A deletion (mtrR promoter) mutations, were associated with elevated ESC MICs. A2059G and C2611T mutations in 23S rRNA were associated with HLAzi-R and azithromycin MICs of 4-32 mg/L, respectively. The 43 whole-genome sequenced isolates belonged to 31 NG-MAST STs. All HLAzi-R isolates belonged to MLST ST1580 and some clonal clustering was observed; however, the isolates differed significantly from the published HLAzi-R isolates from the ongoing UK outbreak. There is good correlation between previously described genetic antimicrobial resistance determinants and phenotypic susceptibility categories for ESCs and azithromycin in N. gonorrhoeae. This work highlights the advantages and potential of whole-genome sequencing to be applied at scale in the surveillance of antibiotic resistant strains of N. gonorrhoeae, both locally and internationally.

Electron and Ion Heating Characteristics during Magnetic Reconnection in the MAST Spherical Tokamak.

Electron and ion heating characteristics during merging reconnection start-up on the MAST spherical tokamak have been revealed in detail using a 130 channel yttrium aluminum garnet (YAG) and a 300 channel Ruby-Thomson scattering system and a new 32 chord ion Doppler tomography diagnostic. Detailed 2D profile measurements of electron and ion temperature together with electron density have been achieved for the first time and it is found that electron temperature forms a highly localized hot spot at the X point and ion temperature globally increases downstream. For the push merging experiment when the guide field is more than 3 times the reconnecting field, a thick layer of a closed flux surface form by the reconnected field sustains the temperature profile for longer than the electron and ion energy relaxation time ~4-10 ms, both characteristic profiles finally forming a triple peak structure at the X point and downstream. An increase in the toroidal guide field results in a more peaked electron temperature profile at the X point, and also produces higher ion temperatures at this point, but the ion temperature profile in the downstream region is unaffected.

Electron-ion equilibration in ultrafast heated graphite.

We have employed fast electrons produced by intense laser illumination to isochorically heat thermal electrons in solid density carbon to temperatures of ∼10,000 K. Using time-resolved x-ray diffraction, the temperature evolution of the lattice ions is obtained through the Debye-Waller effect, and this directly relates to the electron-ion equilibration rate. This is shown to be considerably lower than predicted from ideal plasma models. We attribute this to strong ion coupling screening the electron-ion interaction.

Orbital-free density-functional theory simulations of the dynamic structure factor of warm dense aluminum.

Here, we report orbital-free density-functional theory (OF DFT) molecular dynamics simulations of the dynamic ion structure factor of warm solid density aluminum at T=0.5 eV and T=5 eV. We validate the OF DFT method in the warm dense matter regime through comparison of the static and thermodynamic properties with the more complete Kohn-Sham DFT. This extension of OF DFT to dynamic properties indicates that previously used models based on classical molecular dynamics may be inadequate to capture fully the low frequency dynamics of the response function.

Stable isotopes document resource partitioning and effects of forest disturbance on sympatric cheirogaleid lemurs.

The future of Madagascar's forests and their resident lemurs is precarious. Determining how species respond to forest fragmentation is essential for management efforts. We use stable isotope biogeochemistry to investigate how disturbance affects resource partitioning between two genera of cheirogaleid lemurs (Cheirogaleus and Microcebus) from three humid forest sites: continuous and fragmented forest at Tsinjoarivo, and selectively logged forest at Ranomafana. We test three hypotheses: (H1) cheirogaleids are unaffected by forest fragmentation, (H2) species respond individually to disturbance and may exploit novel resources in fragmented habitat, and (H3) species alter their behavior to rely on the same key resource in disturbed forest. We find significant isotopic differences among species and localities. Carbon data suggest that Microcebus feed lower in the canopy than Cheirogaleus at all three localities and that sympatric Cheirogaleus crossleyi and C. sibreei feed at different canopy heights in the fragmented forest. Microcbus have higher nitrogen isotope values than Cheirogaleus at all localities, indicating more faunivory. After accounting for baseline isotope values in plants, our results provide the most support for H3. We find similar isotopic variations among localities for both genera. Small differences in carbon among localities may reflect shifts in diet or habitat use. Elevated nitrogen values for cheirogaleid lemurs in fragments may reflect increased arthropod consumption or nutritional stress. These results suggest that cheirogaleids are affected by forest disturbance in Eastern Madagascar and stress the importance of accounting for baseline isotopic differences in plants in any work comparing localities.

High morbidity and mortality associated with an outbreak of influenza A(H3N2) in a psycho-geriatric facility.

In spring 2008, an influenza A subtype H3N2 outbreak occurred in a long stay psycho-geriatric ward and two wards in the intellectual disability services (IDS), part of a large psychiatric hospital. The attack rate in the index ward was 90% (18/20) for patients and 35% (7/20) for staff. It was 14% (1/7) and 17% (2/12) in the affected IDS wards for patients and 0% (0/20) and 4% (1/25) for staff. Many of the laboratory-confirmed cases did not have a fever >38 °C, a typical sign of influenza. Control measures included oseltamivir treatment for cases and prophylaxis for contacts, standard and droplet infection control precautions, active surveillance for early detection and isolation of potential cases. As a result, the outbreak did not spread throughout the hospital. Although the staff vaccination rate (10%) prior to the outbreak was low, we observed a much lower vaccine effectiveness rate in the patients (11%) than in the staff (100%) in the index ward. Vaccination of residents and staff of such facilities remains the key influenza prevention strategy.

BK virus (BKV) plasma dynamics in patients with BKV-associated hemorrhagic cystitis following allogeneic stem cell transplantation.

INTRODUCTION: The use of real-time polymerase chain reaction testing in the investigation of BK virus (BKV)-associated disease has been widely studied in renal transplant recipients; however, far less research has been done in this area with respect to the plasma BK viral load dynamics of BKV hemorrhagic cystitis (BKV-HC) in hematopoietic stem cell transplant recipients. AIM: The aim of this study was to examine the BK viral load dynamics in plasma samples collected from patients post transplant who had laboratory-confirmed BKV-HC. METHODS: Patients who developed BK viremia were compared with patients who did not develop viremia, and a statistical comparison of risk factors for viremia was performed. Seventeen patients were included in this study. Urine samples from the day of BKV diagnosis were available in 13 of the 17 cases. In total, 154 archived plasma samples from around the time of the BKV-HC event were also included in the study from these 17 patients. RESULTS: The median time from transplantation to the onset of detectable viremia was 68 days. The median viral load in the 13 urine samples was 1.8 × 10(8) copies/mL, which was significantly higher than the median viral load in the 38 positive plasma samples of 6.6 × 10(2) copies/mL (Mann-Whitney test, U = 16, P < 0.001). CONCLUSION: The lymphocyte count on the day of the positive BKV test was significantly lower in patients with BKV viremia than in patients with no viremia (P = 0.02) and also the white cell and platelet counts were lower on the day of the first positive BKV test. Although there is not inter-patient consistency as regards correlation between urinary BK viral loads and severity of clinical BKV-HC, in individual patients the decline in viral load in plasma did correlate with clinical recovery.

Inelastic x-ray scattering from shocked liquid deuterium.

The Fermi-degenerate plasma conditions created in liquid deuterium by a laser-ablation-driven shock wave were probed with noncollective, spectrally resolved, inelastic x-ray Thomson scattering employing Cl Ly(α) line emission at 2.96 keV. These first x-ray Thomson scattering measurements of the microscopic properties of shocked deuterium show an inferred spatially averaged electron temperature of 8±5 eV, an electron density of 2.2(±0.5)×10(23) cm(-3), and an ionization of 0.8 (-0.25, +0.15). Two-dimensional hydrodynamic simulations using equation-of-state models suited for the extreme parameters occurring in inertial confinement fusion research and planetary interiors are consistent with the experimental results.

Molecular detection and confirmation of Neisseria gonorrhoeae in urogenital and extragenital specimens using the Abbott CT/NG RealTime assay and an in-house assay targeting the porA pseudogene.

Culture for detection of Neisseria gonorrhoeae (NG) is being replaced by molecular assays, but difficulties are observed with false positive and negatives results, especially for extragenital samples. This study evaluates the Abbott CT/NG Real-Time assay and a real-time porA pseudogene assay. Samples (n = 600) from a mixed prevalence Irish population include 164 male urines with corresponding urethral swabs, 58 endocervical swabs, 173 male pharyngeal swabs, 205 male rectal swabs, 36 NG clinical isolates and 26 commensal Neisseria species isolates. There was a 100% concordance between the Abbott CT/NG Real-Time and the porA assay. The positivity rate was 1.2%, 1.7%, 8.1% and 5.8% for FVU/urethral swabs, endocervical, pharyngeal and rectal swabs, respectively. These results were compared to culture and discrepancies were found with nine pharyngeal and three rectal swabs. Seven of the 12 discrepant positive samples were sequenced and were confirmed "true positives". The sensitivity and specificity of the molecular assays was 100%. The sensitivity of the culture-based testing was 100% for urogenital samples but 36% and 75% for pharyngeal and rectal swabs, respectively. The combined Abbott CT/NG and porA assays provide a valuable alternative to culture and also generate a significant increase in the diagnosis of pharyngeal and rectal NG infection.

Emergence and phylogenetic analysis of amantadine-resistant influenza a subtype H3N2 viruses in Dublin, Ireland, over Six Seasons from 2003/2004 to 2008/2009.

OBJECTIVES: To determine the prevalence of amantadine-resistant influenza A viruses and perform genetic analysis of isolates collected in Dublin during six seasons (2003/2004 to 2008/2009). METHODS: Known mutations in the matrix 2 gene (M2) conferring amantadine resistance were screened and phylogenetic analysis of the haemagglutinin gene (HA) performed. RESULTS: Of 1,180 samples, 67 influenza A viruses were isolated, 88% of which were subtype H3N2. Amantadine resistance was only found in subtype H3N2 and increased dramatically from 7% in 2003/2004 to 90% in 2008/2009. A maximum likelihood tree of the HA gene of influenza A H3N2 isolates differentiated them into two distinct clades, clade N and clade S, where the majority of isolates were amantadine-resistant and amantadine-sensitive, respectively. The clades were distinguished by amino acid substitutions, S193F and D225N, which probably conferred a selective advantage for the spread of such viruses. Phylogenetic analysis showed some degree of antigenic drift when compared with the vaccine strain of the corresponding season. CONCLUSIONS: This study showed that circulation in Ireland of a distinct lineage, clade N, among H3N2 viruses favoured emergence of amantadine resistance. Furthermore, comparison of circulating Irish viruses and vaccine strains used in the northern hemisphere showed high similarity.

First isolation and outbreak of OXA-48-producing Klebsiella pneumoniae in an Irish hospital, March to June 2011.

Five OXA-48-producing Klebsiella pneumoniae were detected in a tertiary referral hospital in Ireland between March and June 2011. They were found in the clinical isolates of five cases that were inpatients on general surgical wards. None of the cases had received healthcare at a facility outside of Ireland in the previous 12 months. This is the first report of OXA-48-producing K. pneumoniae in Ireland.

Ex vivo monitoring of human cytomegalovirus-specific CD8(+) T-Cell responses using the QuantiFERON-CMV assay in allogeneic hematopoietic stem cell transplant recipients attending an Irish hospital.

Reconstitution of human cytomegalovirus (HCMV) T-cell immunity is crucial in hematopoietic stem cell transplant (HSCT) recipients. The QuantiFERON-CMV assay for cellular HCMV-specific immunity was evaluated in allogeneic HSCT recipients (n = 43) and patients with hematological malignancies (n = 29) attending a tertiary-care Irish hospital. An intracellular cytokine (ICC) assay correlated with the QuantiFERON-CMV assay. Although there was agreement between HCMV seropositivity and QuantiFERON-CMV assay, six HCMV seropositive immunosuppressed patients with hematological malignancy had negative QuantiFERON-CMV results. The 43 HSCT recipients were classified as high risk (D(-)/R(+)) (n = 18), intermediate risk (D(+)/R(+) and D(+)/R(-)) (n = 17), and low risk (D(-)/R(-)) (n = 8). During episodes of HCMV DNAemia no evidence of HCMV-specific immunity was found using the QuantiFERON-CMV assay. Furthermore, the recovery of HCMV-specific CD8(+) T-cell responses in high-risk seropositive recipients of matched unrelated donors was severely delayed, a mean of 200 (SD = 117) days compared to 58 (SD = 23) days for sibling donors (P < or = 0.028). In addition, three patients with late HCMV infection (infection >100 days post-transplant) had delayed reconstitution of HCMV-specific CD8(+) T cells. Interestingly, two recipients (R(+)/D(-)) developed rapid immune reconstitution by days 15 and 36 post-HSCT, suggesting HCMV-specific T-cell lymphopoiesis of recipient origin. Levels of CD8(+) T-cell immunity in HCMV seropositive HSCT recipients were lowest following HSCT. A high number (33%) of indeterminate results was observed immediately after transplantation. Patients with indeterminate QuantiFERON-CMV results had low levels of HCMV-specific CD8(+) T cells. J. Med. Virol. 82:433-440, 2010. (c) 2010 Wiley-Liss, Inc.

Molecular characterization of carbapenem-resistant Acinetobacter species in an Irish university hospital: predominance of Acinetobacter genomic species 3.

A 30 month prospective study of Acinetobacter species encountered in the Central Pathology Laboratory of St James's Hospital, Dublin, Ireland, was conducted to investigate the prevalence and molecular epidemiology of carbapenem resistance in such isolates. Acinetobacter genomic species 3 (AG3) was found to be the predominant Acinetobacter species (45/114, 39 %) in our institution. A total of 11 % of all Acinetobacter species (12/114) and 22 % of AG3 isolates (10/45) were carbapenem resistant. Carbapenem resistance was mediated by Ambler class D beta-lactamase OXA-23 in all 12 isolates, with insertion sequence ISAba1 found upstream of bla(OXA-23). ISAba1 was also found upstream of bla(ADC-25), which encodes the enzyme AmpC, in an Acinetobacter baumannii isolate, and upstream of the aminoglycoside-acetyltransferase-encoding gene aacC2 in three AG3 isolates. Inter-species plasmidic transfer was most likely involved in the emergence and spread of bla(OXA-23) among the Acinetobacter isolates within our institution. The emergence of carbapenem resistance was associated not only with prior carbapenem use but also with the use of other antimicrobial agents, most notably beta-lactam/beta-lactamase-inhibitor combinations. The study demonstrated the emerging trend of carbapenem resistance in the wider context of the Acinetobacter genus, and reiterated the paramount importance of the prudent use of antimicrobial agents, stringent infection control measures and resistance surveillance of pathogens.

First identification of class A carbapenemase-producing Klebsiella pneumoniae in the Republic of Ireland.

The Klebsiella pneumoniae carbapenemase (KPC) was detected in a carbapenem-resistant respiratory isolate of Klebsiella pneumoniae in an Irish hospital. This is the first report of a KPC-producing isolate in the Republic of Ireland. The isolate was resistant to all beta-lactams. Furthermore, it had reduced susceptibility to three other classes of non-beta-lactam antibiotics. The isolate was not associated with travel abroad. Detection of KPC-producing bacteria has important infection control and public health implications.

Molecular characterization of hepatitis B virus (HBV) isolates, including identification of a novel recombinant, in patients with acute HBV infection attending an Irish hospital.

Hepatitis B virus (HBV) is known to show significant genetic diversity. There are eight HBV genotypes (A-H) characterized by distinct geographical distribution. Mutations in the HBV genome, in particular precore (PC) and basal core promoter (BCP) mutations, may be important factors in the pathogenesis of disease. In this study genetic heterogeneity and phylogenetic analysis of HBV isolates from 32 naïve patients with acute HBV infection was investigated. Eleven patients presented with severe infection, while the remaining 21 had self-limiting illness. Only four isolates from patients with severe HBV infection harbored the G1896A stop codon mutation. One isolate (Irish-13), collected from a patient with acute asymptomatic infection, had a G1896A mutation and a 243 bp deletion of the polymerase gene. A triple mutation, T1753C/A1762T/G1764A was identified in only one isolate (Irish-3) associated with severe infection. The latter also had a mutation, A2339G, in the core gene, not previously reported in severe acute infection caused by genotype D. Variations within the S gene were identified in 6 isolates, including Gly145Ala, associated with vaccine immune escape, Asp144Glu, Ser143Leu and Phe134Leu, each associated with failure to detect HBsAg. Phylogenetic analysis was determined using amplicons of the S gene (678 bp) and distal-X/PC region (672 bp). Genotype A was the most common (75%), followed by genotype D (15.6%), and equal proportions of C, E, F, and H. A novel recombinant of genotypes D and E was identified in an isolate originating from West Africa. Genetic heterogeneity of HBV isolates of HBV isolates from patients with acute infection needs further study of its significance.