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Background: Microscopy is the gold standard for malaria diagnosis but is dependent on trained personnel. Rapid diagnostic tests (RDTs) form the mainstay of diagnosis in endemic areas without access to high-quality microscopy. We aimed to evaluate whether RDT alone could rule out imported malaria in children presenting to UK emergency departments (EDs)., Methods: UK-based, multi-center, retrospective, diagnostic accuracy study. Included: any child <16 years presenting to ED with history of fever and travel to a malaria-endemic country, between 01/01/2016 and 31/12/2017. Diagnosis: microscopy for malarial parasites (clinical reference standard) and RDT (index test). UK Health Research Authority approval: 20/HRA/1341., Results: There were 47 cases of malaria out of 1,414 eligible cases (prevalence 3.3%) in a cohort of children whose median age was 4 years (IQR 2-9), of whom 43% were female. Cases of Plasmodium falciparum totaled 36 (77%, prevalence 2.5%). The sensitivity of RDT alone to detect malaria infection due to any Plasmodium species was 93.6% (95% CI 82.5-98.7%), specificity 99.4% (95% CI 98.9-99.7%), positive predictive value 84.6% (95% CI 71.9-93.1%) and negative predictive value 99.8% (95% CI 99.4-100.0%). Sensitivity of RDT to detect P. falciparum infection was 100% (90.3-100%), specificity 98.8% (98.1-99.3%), positive predictive value 69.2% (54.9-81.2%, n = 46/52) and negative predictive value 100% (99.7-100%, n = 1,362/1,362)., Conclusions: RDTs were 100% sensitive in detecting P. falciparum malaria. However, lower sensitivity for other malaria species and the rise of pfhrp2 and pfhrp3 (pfhrp2/3) gene deletions in the P. falciparum parasite mandate the continued use of microscopy for diagnosing malaria., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.)

The United Kingdom has a national immunization programme which includes annual influenza vaccination in school-aged children, using live attenuated influenza vaccine (LAIV). LAIV is given annually, and it is unclear whether repeat administration can affect immunogenicity. Because LAIV is delivered intranasally, pre-existing local antibody might be important. In this study, we analysed banked samples from a study performed during the 2017/18 influenza season to investigate the role of pre-existing influenza-specific nasal immunoglobulin (Ig)A in children aged 6-14 years. Nasopharyngeal swabs were collected prior to LAIV immunization to measure pre-existing IgA levels and test for concurrent upper respiratory tract viral infections (URTI). Oral fluid samples were taken at baseline and 21-28 days after LAIV to measure IgG as a surrogate of immunogenicity. Antibody levels at baseline were compared with a pre-existing data set of LAIV shedding from the same individuals, measured by reverse transcription-polymerase chain reaction. There was detectable nasal IgA specific to all four strains in the vaccine at baseline. However, baseline nasal IgA did not correlate with the fold change in IgG response to the vaccine. Baseline nasal IgA also did not have an impact upon whether vaccine virus RNA was detectable after immunization. There was no difference in fold change of antibody between individuals with and without an URTI at the time of immunization. Overall, we observed no effect of pre-existing influenza-specific nasal antibody levels on immunogenicity, supporting annual immunization with LAIV in children., (© 2021 British Society for Immunology.)

Background: The (H1N1)pdm09 live attenuated influenza vaccine (LAIV) strain was changed for the 2017-2018 influenza season to improve viral fitness, following poor protection against (H1N1)pdm09 viruses in 2015-2016. We conducted LAIV virus shedding studies to assess the effect of this change., Methods: Children aged 2-18 years were recruited to receive LAIV in the 2016-2017 (n = 641) and 2017-2018 (n = 362) influenza seasons. Viruses from nasal swabs taken 1, 3, and 6 days postvaccination were quantified by reverse-transcription polymerase chain reaction and area under the curve titers were determined. Presence and quantity of shedding were compared between strains and seasons with adjustment for age and prior LAIV (n = 436), inactivated seasonal vaccine (n = 100), or (H1N1)pdm09 vaccine (n = 166) receipt., Results: (H1N1)pdm09 detection (positivity) in 2016-2017 and 2017-2018 (11.2% and 3.9%, respectively) was lower than that of H3N2 (19.7% and 18.7%, respectively) and B/Victoria (28.9% and 33.9%, respectively). (H1N1)pdm09 positivity was higher in 2016-2017 than 2017-2018 (P = .005), but within shedding-positive participants, the (H1N1)pdm09 titer increased in 2017-2018 (P = .02). H3N2 and influenza B titers were similar between seasons. Positivity declined with age, and prior vaccination reduced the likelihood of shedding influenza B but not (H1N1)pdm09., Conclusions: The (H1N1)pdm09 titer increased in 2017-2018, indicating more efficient virus replication in shedding-positive children than the 2016-2017 strain, although overall positivity was reduced. Age and vaccination history require consideration when correlating virus shedding and protection., Clinical Trials Registration: NCT02143882, NCT02866942, and NCT03104790., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Different vaccine strains included in the live attenuated influenza vaccine (LAIV) have variable efficacy. The reasons for this are not clear and may include differences in immunogenicity. We report a Phase IV open-label study on the immunogenicity of a single dose of quadrivalent LAIV (Fluenz™ Tetra) in children during the 2015/16 season, to investigate the antibody responses to different strains. Eligible children were enrolled to receive LAIV; nasal samples were collected before and approximately 4 weeks after immunization. There was a significant increase in nasal immunoglobulin (Ig)A to the H3N2, B/Victoria lineage (B/Brisbane) and B/Yamagata lineage (B/Phuket) components, but not to the H1N1 component. The fold change in nasal IgA response was inversely proportional to the baseline nasal IgA titre for H1N1, H3N2 and B/Brisbane. We investigated possible associations that may explain baseline nasal IgA, including age and prior vaccination status, but found different patterns for different antigens, suggesting that the response is multi-factorial. Overall, we observed differences in immune responses to different viral strains included in the vaccine; the reasons for this require further investigation., (© 2019 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.)

Background: Point-of-care tests (POCTs) for influenza are diagnostically superior to clinical diagnosis, but their impact on patient outcomes is unclear., Methods: A systematic review of influenza POCTs versus usual care in ambulatory care settings. Studies were identified by searching six databases and assessed using the Cochrane risk of bias tool. Estimates of risk ratios (RR), standardised mean differences, 95% confidence intervals and I2 were obtained by random effects meta-analyses. We explored heterogeneity with sensitivity analyses and meta-regression., Results: 12,928 citations were screened. Seven randomized studies (n = 4,324) and six non-randomized studies (n = 4,774) were included. Most evidence came from paediatric emergency departments. Risk of bias was moderate in randomized studies and higher in non-randomized studies. In randomized trials, POCTs had no effect on admissions (RR 0.93, 95% CI 0.61-1.42, I2 = 34%), returning for care (RR 1.00 95% CI = 0.77-1.29, I2 = 7%), or antibiotic prescribing (RR 0.97, 95% CI 0.82-1.15, I2 = 70%), but increased prescribing of antivirals (RR 2.65, 95% CI 1.95-3.60; I2 = 0%). Further testing was reduced for full blood counts (FBC) (RR 0.80, 95% CI 0.69-0.92 I2 = 0%), blood cultures (RR 0.82, 95% CI 0.68-0.99; I2 = 0%) and chest radiography (RR 0.81, 95% CI 0.68-0.96; I2 = 32%), but not urinalysis (RR 0.91, 95% CI 0.78-w1.07; I2 = 20%). Time in the emergency department was not changed. Fewer non-randomized studies reported these outcomes, with some findings reversed or attenuated (fewer antibiotic prescriptions and less urinalysis in tested patients)., Conclusions: Point-of-care testing for influenza influences prescribing and testing decisions, particularly for children in emergency departments. Observational evidence shows challenges for real-world implementation., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: A number of point-of-care diagnostic tests are commercially available in the UK, however, not much is known regarding GPs' desire for these tests or the clinical areas of interest., Objective: We sought to establish for which conditions point-of-care tests (POCTs) would be most helpful to UK GPs for diagnosis, reduction of referrals, and monitoring of chronic conditions., Methods: A total of 1635 regionally representative GPs were invited to complete an online cross-sectional survey between 31 September and 16 October 2012., Results: A total of 1109 (68%) GPs responded to the survey. The most frequently cited conditions were urinary tract infections for diagnosis (47% of respondents), pulmonary embolism/deep vein thrombosis for referral reduction (47%) and international normalized ratio/anticoagulation for monitoring (49%)., Conclusions: This survey has identified the conditions for which UK GPs would find POCTs most helpful. Comments by respondents suggest that quite radical system-level adjustments will be required to allow primary care clinicians to capitalize on the potential benefits of POCTs., (© The Author 2016. Published by Oxford University Press.)

Objectives: The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) programme is a longitudinal global surveillance study to monitor in vitro data on microbial susceptibility in centres that prescribe meropenem. This overview provides data on the susceptibility of Gram-negative bacteria (n = 1300) isolated from clinical specimens of children hospitalized in a paediatric intensive care unit (ICU) during 1997-2007., Methods: MICs of meropenem and eight other antibiotics were determined using the CLSI agar dilution method., Results: Meropenem, imipenem and ciprofloxacin were most active (>90% susceptibility) against the tested isolates. A greater proportion of Pseudomonas aeruginosa isolates was susceptible to meropenem compared with imipenem. Antibiotic susceptibility of Enterobacteriaceae and Acinetobacter baumannii showed an increase in 2007. Only susceptibility of P. aeruginosa to ceftazidime and cefepime increased. The incidence of extended-spectrum beta-lactamase (ESBL) producers among Enterobacteriaceae isolates decreased from 37% in 1997 to 21.8% in 2007, and AmpC beta-lactamase producers decreased from 24.6% to 5.7%. Consumption of cephalosporins remained the same and piperacillin/tazobactam increased 3-fold. During 11 years, despite an increase in carbapenem consumption, meropenem and imipenem have retained excellent activity against the majority of isolates studied., Conclusions: The comparison of antibiotic susceptibility of Gram-negative isolates in 1997 and 2007 showed a trend of increase, and the number of beta-lactamase-producing isolates among Enterobacteriaceae showed a trend of decrease possibly related to changes in antibiotic policy.

The first beta-lactamase was identified in an isolate of Escherichia coli in 1940. To date, there are >130 TEM-type and >50 sulfhydryl variable (SHV)-type beta-lactamases, mainly in E. coli, Klebsiella pneumoniae, and Proteus mirabilis but also in other members of the Enterobacteriaceae family and in some nonenteric organisms, such as Acinetobacter species. The incidence of expanded-spectrum beta-lactamases (ESBLs) varies, depending on which area of the globe the isolates originate from. ESBLs render the oxyimino-cephalosporins ineffective, and ESBL-producing organisms frequently also possess resistance factors to other classes of antibiotics, such as aminoglycosides and fluoroquinolones, and possibly also piperacillin-tazobactam and cefepime. These results suggest that microbiology laboratories should routinely test for the presence of these strains among their isolates and that the antibiotics of choice for infections believed to be caused by these types of organisms are the carbapenems.

Objectives: The Optimising Pharmacodynamic Target Attainment using the MYSTIC (Meropenem Yearly Susceptibility Test Information Collection) Antibiogram (OPTAMA) programme identifies antibiotic regimens with the highest probability of attaining critical pharmacodynamic targets, accounting for the inherent variability in pharmacokinetics, dosages and MIC distributions., Methods: European MIC data were obtained from the MYSTIC programme. Pharmacodynamic target attainment was calculated by Monte Carlo simulation for meropenem, imipenem, ceftazidime, cefepime, piperacillin/tazobactam and ciprofloxacin against Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa., Results: Significant differences in probability of target attainment were found, with Northern Europe demonstrating the highest probabilities of target attainment and Eastern Europe the lowest. The carbapenems had the highest target attainments and susceptibility levels across all regions and pathogens. The cephalosporins demonstrated high target attainments and susceptibility results against E. coli and K. pneumoniae in Northern and Southern Europe. Piperacillin/tazobactam and ciprofloxacin had the lowest levels for both parameters in all regions. Desirable target attainment was not achieved (except for carbapenems in Northern Europe) for A. baumannii and P. aeruginosa; thus, combination therapy may be appropriate empirical therapy for these pathogens in Southern and Eastern Europe. The closest correlations between target attainment and susceptibility were for meropenem 1 g every 8 h, imipenem 0.5 g every 6 h and ceftazidime 1 g every 8 h., Conclusions: The study highlighted significant overestimations between the probability of target attainment and the reported percentage susceptibility, particularly for piperacillin/tazobactam and ciprofloxacin. The approach of the OPTAMA programme provides a novel tool which complements susceptibility data to help in the selection of appropriate empirical antibiotic therapy.

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) is a global, multicentre surveillance study that compares the activity of meropenem in centres that are prescribers with that of imipenem, ceftazidime, piperacillin/tazobactam, ciprofloxacin and gentamicin. Of the 46 centres (intensive care units, cystic fibrosis units, neutropenia units and general wards) contributing to this study, 29 were in Europe, 14 in the Americas and three in the Middle East and Asia. The results for the most common isolates obtained in the first year of the study from these three regions show that meropenem has a broad spectrum of activity and potency in these centres, with 89% of the 6890 strains tested having an MIC < or = 4 mg/L. The overall susceptibility was lower for the comparator antibiotics. There was evidence in all regions of strains producing beta-lactamases and other resistance mechanisms against the other beta-lactams tested, fluoroquinolones and aminoglycosides. Future years' results from this surveillance study will show whether meropenem will continue to exhibit such activity.

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) is a global, multicentre surveillance study that compares the activity of meropenem in centres that are prescribers with that of imipenem, ceftazidime, piperacillin/tazobactam, ciprofloxacin and gentamicin. Of the 46 centres (intensive care units, cystic fibrosis units, neutropenia units and general wards) contributing to this study, 29 were in Europe, 14 in the Americas and three in the Middle East and Asia. The results for the most common isolates obtained in the first year of the study from these three regions show that meropenem has a broad spectrum of activity and potency in these centres, with 89% of the 6890 strains tested having an MIC 4 mg/L. The overall susceptibility was lower for the comparator antibiotics. There was evidence in all regions of strains producing beta-lactamases and other resistance mechanisms against the other beta-lactams tested, fluoroquinolones and aminoglycosides. Future years' results from this surveillance study will show whether meropenem will continue to exhibit such activity.

Meropenem body fluid and tissue concentration data from both published studies and samples obtained during efficacy evaluation have been compiled and presented according to a consistent format to facilitate comparison. The concentration data have been compared with the mode MIC data available for the pathogens isolated during the clinical evaluation of meropenem. These data support the widespread and rapid penetration of meropenem into the interstitial fluid of those tissues not protected by a tight epithelial barrier. Furthermore, they suggest that the proposed dosages of meropenem 500 mg or 1 g tds would provide an adequate duration of cover at tissue sites for the treatment of a range of commonly occurring pathogens. A higher dosage of 40 mg/kg or 2 g in adults given tds would be recommended for meningitis based on the penetration of meropenem into CSF. Overall, the tissue and body fluid data presented confirm the expectation, based on the plasma concentrations and theoretical arguments, that meropenem is rapidly and readily distributed into the interstitial fluid, thereby producing concentrations in tissues likely to be clinically effective. This is consistent with the available clinical data on the therapeutic efficacy of meropenem.

A clinical trial comparing a conventional adhesive, Concise, with a new fluoride-containing composite cement is described. The bond failure rate, plaque score, gingival health, and enamel decalcification were assessed for each material after a minimum period of 1 year. The preliminary results show no significant difference between the two materials for each of the variables examined, although there was a reduction in the number of white spot lesions using the fluoride-containing composite. The level of fluoride ion concentration required to inhibit the growth of oral micro-organisms is discussed.

A computer-assisted learning (CAL) package developed for undergraduate teaching in orthodontics is described. The programme makes use of the principle of 'hypertext'. The ability of undergraduates to learn from the programme is evaluated and compared to students taught conventionally. The opinions of the undergraduates who tried the programme are sought and discussed.

As part of a multidisciplinary study into the health effects of solvents, workplace assessments and airborne solvent vapour monitoring was conducted in 46 spray painting workshops in the Sydney metropolitan area. Breathing-zone samples were taken from 50 apprentices and 14 experienced spray painters. An interview schedule was developed to obtain information about the use of acrylic or two-pack paint systems, the use of engineering controls, the use of personal protective equipment and the availability of material safety data sheets. Contaminants typical of the chemical products used in this industry were encountered (aromatic hydrocarbons, C5-C7 aliphatic hydrocarbons, ketones, esters). The results of airborne solvent monitoring indicate a total solvent exposure in the range 1-99% of a combined Worksafe Australia exposure standard, with a mean of 19%. Solvent exposure was highest when spraying acrylic paint in the open workshop and lowest when spraying two pack paint in a spray booth. Much the same personal protective equipment was available in all workshops, but wide variation in its use was observed. Material safety data sheets were not observed in any of the workshops.