Evolutionary clade affects resistance of Clostridium difficile spores to Cold Atmospheric Plasma

Clostridium difficile is a spore forming bacterium and the leading cause of colitis and antibiotic associated diarrhoea in the developed world. Spores produced by C. difficile are robust and can remain viable for months, leading to prolonged healthcare-associated outbreaks with high mortality. Exposure of C. difficile spores to a novel, non-thermal atmospheric pressure gas plasma was assessed. Factors affecting sporicidal efficacy, including percentage of oxygen in the helium carrier gas admixture, and the effect on spores from different strains representing the five evolutionary C. difficile clades was investigated. Strains from different clades displayed varying resistance to cold plasma. Strain R20291, representing the globally epidemic ribotype 027 type, was the most resistant. However all tested strains displayed a ~3 log reduction in viable spore counts after plasma treatment for 5 minutes. Inactivation of a ribotype 078 strain, the most prevalent clinical type seen in Northern Ireland, was further assessed with respect to surface decontamination, pH, and hydrogen peroxide concentration. Environmental factors affected plasma activity, with dry spores without the presence of organic matter being most susceptible. This study demonstrates that cold atmospheric plasma can effectively inactivate C. difficile spores, and highlights factors that can affect sporicidal activity

Ethnic differences in the clustering and outcomes of health behaviours during pregnancy: results from the Born in Bradford cohort

OBJECTIVE. Pregnancy is a time of optimal motivation for many women to make positive behavioural changes. We aim to describe pregnant women with similar patterns of self-reported health behaviours and examine associations with birth outcomes. METHODS. We examined the clustering of multiple health behaviours during pregnancy in the Born in Bradford cohort, including smoking physical inactivity, vitamin d supplementation, and exposure to second hand smoke. Latent class analysis was used to identify groups of individuals with similar patterns of health behaviours separately for White British (WB) and Pakistani mothers. Multinomial regression was then used to examine the association between group membership and birth outcomes, which included preterm birth and mean birth weight. RESULTS. For WB mothers, offspring of those in the ‘Unhealthiest’ group had lower mean birth weight than those in the ‘Mostly healthy but inactive’ class, although no association was observed for preterm birth. For Pakistani mothers, group membership was not associated with birth weight differences, although the odds of preterm birth was higher in ‘Inactive smokers’ compared to the ‘Mostly healthy but inactive’ group. CONCLUSION. The use of latent class methods provides important information about the clustering of health behaviours which can be used to target population segments requiring behaviour change interventions considering multiple risk factors. Given the dominant negative association of smoking with the birth outcomes investigated, latent class groupings of other health behaviours may not confer additional risk information for these outcomes

Terrisporobacter hibernicus sp. nov., isolated from bovine faeces in Northern Ireland

A new species of Terrisporobacter, a Gram-positive, spore-forming anaerobic group, proposed name Terrisporobacter hiberni-cus sp. nov., was isolated in Northern Ireland from bovine faeces collected in 2016. Designated as MCA3T, cells of T. hibernicus sp. nov. are rod shaped and motile. Cells tolerate NaCl from 0.5 to 5.5 % (w/v), with a pH tolerance between pH 6 and 9. The optimal temperature for growth is 35–40 °C, and temperatures from 20 to 30 °C are tolerated. The polar lipid profile displays diphosphatidylglycerol, phosphatidylglycerol, two aminoglycolipids, one glycophospholipid, one aminolipid, three glycolipids, five phospholipids and one lipid. No respiratory quinones are detected. The predominant fatty acid profile includes C16: 0 at 22.8 %. Strain MCA3T is positive for glucose and maltose acidification, as well as glycerol and sorbitol. The biochemical results from a VITEK2 assay of strain MCA3T, Terrisporobacter petrolearius LAM0A37T and Terrisporobacter mayombei DSM 6539T are also included for the first time. The closed and complete genome of strain MCA3T from a hybrid Oxford Nanopore Technology MinION/Illumina assembly reveals no evidence for known virulence genes. Draft genome sequencing of T. mayombei DSM 6539T and T. petrolearius LAM0A37T, as performed by Illumina MiSeq, provides reference genomes for these respective species of Terrisporobacter for the first time. DNA–DNA hybridization values (d4) of MCA3T to Terrisporobacter glycolicus ATCC 14880T, T. petrolearius LAM0A37T and T. mayombei DSM 6539T are 48.8, 67.4 and 46.3 %, with cutoff value at 70 %. The type strain for T. hibernicus sp. nov. is MCA3T (=NCTC 14625T=LMG 32430T)

The "Petechiae in children" (PiC) study: Evaluating potential clinical decision rules for the management of feverish children with non-blanching rashes, including the role of point of care testing for Procalcitonin & Neisseria meningitidis DNA - a stu

© 2018 The Author(s). Background: Children commonly present to Emergency Departments (ED) with a non-blanching rash in the context of a feverish illness. While most have a self-limiting viral illness, this combination of features potentially represents invasive serious bacterial infection, including meningococcal septicaemia. A paucity of definitive diagnostic testing creates diagnostic uncertainty for clinicians; a safe approach mandates children without invasive disease are often admitted and treated with broad-spectrum antibiotics. Conversely, a cohort of children still experience significant mortality and morbidity due to late diagnosis. Current management is based on evidence which predates (i) the introduction of meningococcal B and C vaccines and (ii) availability of point of care testing (POCT) for procalcitonin (PCT) and Neisseria meningitidis DNA. Methods: This PiC study is a prospective diagnostic accuracy study evaluating (i) rapid POCT for PCT and N. meningitidis DNA and (ii) performance of existing clinical practice guidelines (CPG) for feverish children with non-blanching rash. All children presenting to the ED with a history of fever and non-blanching rash are eligible. Children are managed as normal, with detailed prospective collection of data pertinent to CPGs, and a throat swab and blood used for rapid POCT. The study is running over 2years and aims to recruit 300 children. Primary objective: Report on the diagnostic accuracy of POCT for (i) N. meningitidis DNA and (ii) PCT in the diagnosis of early MD Discussion: The PiC study will provide important information for policy makers regarding the value of POCT and on the utility and cost of emerging diagnostic strategies. The study will also identify which elements of existing CPGs may merit inclusion in any future study to derive clinical decision rules for this population

‘If I am on ART, my new-born baby should be put on treatment immediately’: Exploring the acceptability, and appropriateness of Cepheid Xpert HIV-1 Qual assay for early infant diagnosis of HIV in Malawi

Early infant diagnosis of HIV (EID-HIV) is key to reducing paediatric HIV mortality. Traditional approaches for diagnosing HIV in exposed infants are usually unable to optimally contribute to EID. Point-of-care testing such as Cepheid Xpert HIV-1 Qual assay-1 (XPertHIV) are available and could improve EID-HIV in resource constrained and high HIV burden contexts. We investigated the acceptability and perceived appropriateness of XpertHIV for EID-HIV in Mulanje Hospital, Malawi. Qualitative cross-sectional study using semi-structured interviews (SSI) among caregivers and health care workers at Mulanje District Hospital. The qualitative study was nested within a larger diagnostic study that evaluated the performance of XpertHIV using whole-blood-sample in a resource limited and high burden setting. A total of 65 SSIs were conducted among caregivers (n = 60) and health care providers (n = 5). Data were coded using deductive and inductive approaches while thematic approach was used to analyse data. Point-of-care XPertHIV was perceived to be acceptable among caregivers and health care providers. Caregivers’ motivations for accepting XPertHIV HIV-testing for their infants included perceived risk of HIV emanating from child’s exposure and validation of caregiver’s own HIV sero-status. Although concerns about pain of testing and blood sample volumes taken from an infant remained amplified, overall, both caregivers and health care providers felt XpertHIV was appropriate because of its quick result turn-around-time which decreased anxiety and stress, the prospect of early treatment initiation and reduction in hospital visits and related costs. Implementation of XpertHIV has a great potential to improve EID-HIV in Malawi because of its quick turn-around-time and associated benefits including overcoming access-related barriers. Scaled implementation of this diagnostic technology require a robust community engagement strategy for managing caregivers and community myths and misconceptions towards the amount of blood sample collected from infants

Diagnostic test accuracy of point-of-care procalcitonin to diagnose serious bacterial infections in children

Background: The National Institute for Health and Care Excellence (NICE) have called for research into the role of biomarkers, and specifically procalcitonin (PCT), for the early diagnosis of serious bacterial infections (SBI) in children. The aim of this study was to compare the diagnostic test accuracy of C-reactive protein (CRP) and PCT for the diagnosis of SBI in children. Methods: Data was collected prospectively from four UK emergency departments (ED) between November 2017 and June 2019. Consecutive children under 18years of age with fever and features of possible sepsis and/or meningitis were eligible for inclusion. The index tests were PCT and CRP and the reference standard was the confirmation of SBI. Results: 213 children were included in the final analysis. 116 participants (54.5%) were male, and the median age was 2 years, 9months. Parenteral antibiotics were given to 100 (46.9%), three (1.4%) were admitted to a paediatric intensive care unit and there were no deaths. There were ten (4.7%) confirmed SBI. The area under the curve for PCT and CRP for the detection of SBI was identical at 0.70. Conclusions: There was no difference in the performance of PCT and CRP for the recognition of SBI in this cohort. Trial registration: Registered at https://www.clinicaltrials.gov(trial registration: NCT03378258) on the 19th of December 2017

Costing and cost-effectiveness of Cepheid Xpert HIV -1 Qual Assay using whole blood protocol versus PCR by Abbott Systems in Malawi

Background Timely diagnosis of HIV in infants and children is an urgent priority. In Malawi, 40,000 infants annually are HIV exposed. However, gold standard polymerase-chain-reaction (PCR) based testing requires centralised laboratories, causing turn-around times (TAT) of 2 to 3 months and significant loss to follow-up. If feasible and acceptable, minimising diagnostic delays through HIV Point-of-care-testing (POCT) may be cost-effective. We assessed whether POCT Cepheid Xpert HIV-1 Qual assay whole blood (XpertHIV) was more cost-effective than PCR. Methods From July-August 2018, 700 PCR Abbott tests using dried blood spots (DBS) were performed on 680 participants who enrolled on the feasibility, acceptability and performance of the XpertHIV study. Newly identified HIV-positive DBS from the 680 participants were retested, so with confirmatory testing of the HIV-positive cases, 700 tests were performed. We conducted a cost-minimisation and cost-effectiveness analysis of XpertHIV against PCR, as the standard of care. A random sample of 200 caregivers from the 680 participants had semi-structured interviews to explore costs from a societal perspective of XpertHIV at Mulanje District Hospital, Malawi. Analysis used TAT as the primary outcome measure. Results were extrapolated from the study period (29 days) to a year (240 working days). Sensitivity analyses characterised individual and joint parameter uncertainty and estimated patient cost per test. Results During the study period, XpertHIV was cost-minimising at $42.34 per test compared to$66.66 for PCR. Over a year, XpertHIV remained cost-minimising at $16.12 compared to PCR at$27.06. From the patient perspective (travel, food, lost productivity), the cost per test of XpertHIV was $2.45. XpertHIV had a mean TAT of 7.10 hours compared to 153.15 hours for PCR. Extrapolates accounting for equipment costs, lab consumables and losses to follow up estimated annual savings of$2,193,538.88 if XpertHIV is used nationally, as opposed to PCR. Conclusions This preliminary evidence suggests that adopting POCT XpertHIV will save time, allowing HIV-exposed infants to receive prompt care and may improve outcomes. The Malawi government will pay less due to XpertHIV’s cost savings and associated benefits

Evaluation of the impact of universal testing for gestational diabetes mellitus on maternal and neonatal health outcomes: a retrospective analysis

Background: Gestational diabetes (GDM) affects a substantial proportion of women in pregnancy and is associated with increased risk of adverse perinatal and long term outcomes. Treatment seems to improve perinatal outcomes, the relative effectiveness of different strategies for identifying women with GDM however is less clear. This paper describes an evaluation of the impact of a change in policy from selective risk factor based offering, to universal offering of an oral glucose tolerance test (OGTT) to identify women with GDM on maternal and neonatal outcomes. Methods: Retrospective six year analysis of 35,674 births at the Women’s and Newborn unit, Bradford Royal Infirmary, United Kingdom. Results: The proportion of the whole obstetric population diagnosed with GDM increased almost fourfold following universal offering of an OGTT compared to selective offering of an OGTT; Rate Ratio (RR) 3.75 (95% CI 3.28 to 4.29), the proportion identified with severe hyperglycaemia doubled following the policy change; 1.96 (1.50 to 2.58). The case detection rate however, for GDM in the whole population and severe hyperglycaemia in those with GDM reduced by 50-60%; 0.40 (0.35 to 0.46) and 0.51 (0.39 to 0.67) respectively. Universally offering an OGTT was associated with an increased induction of labour rate in the whole obstetric population and in women with GDM; 1.43 (1.35 to 1.50) and 1.21 (1.00 to1.49) respectively. Caesarean section, macrosomia and perinatal mortality rates in the whole population were similar. For women with GDM, rate of caesarean section; 0.70 (0.57 to 0.87), macrosomia; 0.22 (0.15 to 0.34) and perinatal mortality 0.12 (0.03 to 0.46) decreased following the policy change. Conclusions: Universally offering an OGTT was associated with increased identification of women with GDM and severe hyperglycaemia and with neonatal benefits for those with GDM. There was no evidence of benefit or adverse effects in neonatal outcomes in the whole obstetric population