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We examined the feasibility of implementing preventive measures to prevent SARS-CoV-2 transmission across 105 English primary schools in summer 2020 via a survey and interviews with headteachers. High rates of implementation of most recommended measures were noted with the exception of requiring 2 m distance for students, fitting hand sanitizers in classrooms and introducing one-way systems in school corridors. Measures such as regular handwashing and stopping assemblies were considered easy to implement. Majorly challenging measures included distancing between individuals (for students: 51%, N = 99; for staff: 34%; N = 98; for parents: 26%, N = 100), spacing out desks (34%, N = 99), keeping same staff assigned to each student group (33%, N = 97) and staggering break times (25%, N = 99). Rapid implementation was facilitated by staff commitment and communication among stakeholders, but hampered by limitations with guidance received, physical environments, resources, parental adherence and balancing preventive measures with learning. Difficulties with distancing for younger children suggest that smaller bubbles with fewer distancing requirements within these may be a policy option. Schools require further financial, human resource and other support for effective implementation of preventive measures.

Sibstantial progress has been made in the fight against uberculosis (TB); however, new approaches are needed to achieve the current target set by the World Health Organization (WHO) to reduce [...]

Background: Following the full re-opening of schools in England and emergence of the SARS-CoV-2 Alpha variant, we investigated the risk of SARS-CoV-2 infection in students and staff who were contacts of a confirmed case in a school bubble (school groupings with limited interactions), along with their household members. Methods: Primary and secondary school bubbles were recruited into sKIDsBUBBLE after being sent home to self-isolate following a confirmed case of COVID-19 in the bubble. Bubble participants and their household members were sent home-testing kits comprising nasal swabs for RT-PCR testing and whole genome sequencing, and oral fluid swabs for SARS-CoV-2 antibodies. Results: During November-December 2020, 14 bubbles were recruited from 7 schools, including 269 bubble contacts (248 students, 21 staff) and 823 household contacts (524 adults, 299 children). The secondary attack rate was 10.0% (6/60) in primary and 3.9% (4/102) in secondary school students, compared to 6.3% (1/16) and 0% (0/1) among staff, respectively. The incidence rate for household contacts of primary school students was 6.6% (12/183) and 3.7% (1/27) for household contacts of primary school staff. In secondary schools, this was 3.5% (11/317) and 0% (0/1), respectively. Household contacts were more likely to test positive if their bubble contact tested positive although there were new infections among household contacts of uninfected bubble contacts. Interpretation: Compared to other institutional settings, the overall risk of secondary infection in school bubbles and their household contacts was low. Our findings are important for developing evidence-based infection prevention guidelines for educational settings. [ABSTRACT FROM AUTHOR]

To the Editor: Melioidosis is endemic in southern and Southeast Asia and northern Australia. Although relatively few indigenous cases are recognized in the Indian subcontinent, a substantial proportion of cases [...]

Recently, host whole blood gene expression signatures have been identified for diagnosis of tuberculosis (TB). Absolute quantification of the concentrations of signature transcripts in blood have not been reported, but would facilitate diagnostic test development. To identify minimal transcript signatures, we applied a transcript selection procedure to microarray data from African adults comprising 536 patients with TB, other diseases (OD) and latent TB (LTBI), divided into training and test sets. Signatures were further investigated using reverse transcriptase (RT)—digital PCR (dPCR). A four-transcript signature (GBP6, TMCC1, PRDM1 , and ARG1) measured using RT-dPCR distinguished TB patients from those with OD (area under the curve (AUC) 93.8% (CI95% 82.2–100%). A three-transcript signature (FCGR1A, ZNF296, and C1QB) differentiated TB from LTBI (AUC 97.3%, CI95%: 93.3–100%), regardless of HIV. These signatures have been validated across platforms and across samples offering strong, quantitative support for their use as diagnostic biomarkers for TB. [ABSTRACT FROM AUTHOR]

Background: A major impediment to tuberculosis control in Africa is the difficulty in diagnosing active tuberculosis (TB), particularly in the context of HIV infection. We hypothesized that a unique host blood RNA transcriptional signature would distinguish TB from other diseases (OD) in HIV-infected and -uninfected patients, and that this could be the basis of a simple diagnostic test. Methods and Findings: Adult case-control cohorts were established in South Africa and Malawi of HIV-infected or uninfected individuals consisting of 584 patients with either TB (confirmed by culture of Mycobacterium tuberculosis [M.TB] from sputum or tissue sample in a patient under investigation for TB), OD (i.e., TB was considered in the differential diagnosis but then excluded), or healthy individuals with latent TB infection (LTBI). Individuals were randomized into training (80%) and test (20%) cohorts. Blood transcriptional profiles were assessed and minimal sets of significantly differentially expressed transcripts distinguishing TB from LTBI and OD were identified in the training cohort. A 27 transcript signature distinguished TB from LTBI and a 44 transcript signature distinguished TB from OD. To evaluate our signatures, we used a novel computational method to calculate a disease risk score (DRS) for each patient. The classification based on this score was first evaluated in the test cohort, and then validated in an independent publically available dataset (GSE19491). In our test cohort, the DRS classified TB from LTBI (sensitivity 95%, 95% CI [87-100]; specificity 90%, 95% CI [80-97]) and TB from OD (sensitivity 93%, 95% CI [83-100]; specificity 88%, 95% CI [74-97]). In the independent validation cohort, TB patients were distinguished both from LTBI individuals (sensitivity 95%, 95% CI [85-100]; specificity 94%, 95% CI [84-100]) and OD patients (sensitivity 100%, 95% CI [100-100]; specificity 96%, 95% CI [93-100]). Limitations of our study include the use of only culture confirmed TB patients, and the potential that TB may have been misdiagnosed in a small proportion of OD patients despite the extensive clinical investigation used to assign each patient to their diagnostic group. Conclusions: In our study, blood transcriptional signatures distinguished TB from other conditions prevalent in HIV- infected and -uninfected African adults. Our DRS, based on these signatures, could be developed as a test for TB suitable for use in HIV endemic countries. Further evaluation of the performance of the signatures and DRS in prospective populations of patients with symptoms consistent with TB will be needed to define their clinical value under operational conditions. Please see later in the article for the Editors' Summary., Introduction There is an urgent need for improved tests to diagnose active tuberculosis (TB), particularly in countries of sub-Saharan Africa most affected by the TB/HIV pandemic. The diagnosis of TB [...]

Background: Sepsis is a common cause of serious illness and death. Sepsis management remains challenging and suboptimal. To support rapid sepsis diagnosis and treatment, screening tools have been embedded into hospital digital systems to appear as digital alerts. The implementation of digital alerts to improve the management of sepsis and deterioration is a complex intervention that has to fit with team workflow and the views and practices of hospital staff. Despite the importance of human decision-making and behavior in optimal implementation, there are limited qualitative studies that explore the views and experiences of health care professionals regarding digital alerts as sepsis or deterioration computerized clinician decision support systems (CCDSSs)., Objective: This study aims to explore the views and experiences of health care professionals on the use of sepsis or deterioration CCDSSs and to identify barriers and facilitators to their implementation and use in National Health Service (NHS) hospitals., Methods: We conducted a qualitative, multisite study with unstructured observations and semistructured interviews with health care professionals from emergency departments, outreach teams, and intensive or acute units in 3 NHS hospital trusts in England. Data from both interviews and observations were analyzed together inductively using thematic analysis., Results: A total of 22 health care professionals were interviewed, and 12 observation sessions were undertaken. A total of four themes regarding digital alerts were identified: (1) support decision-making as nested in electronic health records, but never substitute professionals' knowledge and experience; (2) remind to take action according to the context, such as the hospital unit and the job role; (3) improve the alerts and their introduction, by making them more accessible, easy to use, not intrusive, more accurate, as well as integrated across the whole health care system; and (4) contextual factors affecting views and use of alerts in the NHS trusts. Digital alerts are more optimally used in general hospital units with a lower senior decision maker:patient ratio and by health care professionals with experience of a similar technology. Better use of the alerts was associated with quality improvement initiatives and continuous sepsis training. The trusts' features, such as the presence of a 24/7 emergency outreach team, good technological resources, and staffing and teamwork, favored a more optimal use., Conclusions: Trust implementation of sepsis or deterioration CCDSSs requires support on multiple levels and at all phases of the intervention, starting from a prego-live analysis addressing organizational needs and readiness. Advancements toward minimally disruptive and smart digital alerts as sepsis or deterioration CCDSSs, which are more accurate and specific but at the same time scalable and accessible, require policy changes and investments in multidisciplinary research., (©Runa Lazzarino, Aleksandra J Borek, Kate Honeyford, John Welch, Andrew J Brent, Anne Kinderlerer, Graham Cooke, Shashank Patil, Anthony Gordon, Ben Glampson, Philippa Goodman, Peter Ghazal, Ron Daniels, Céire E Costelloe, Sarah Tonkin-Crine. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 15.10.2024.)

Sepsis is a worldwide public health problem. Rapid identification is associated with improved patient outcomes-if followed by timely appropriate treatment., Objectives: Describe digital sepsis alerts (DSAs) in use in English National Health Service (NHS) acute hospitals., Methods: A Freedom of Information request surveyed acute NHS Trusts on their adoption of electronic patient records (EPRs) and DSAs., Results: Of the 99 Trusts that responded, 84 had an EPR. Over 20 different EPR system providers were identified as operational in England. The most common providers were Cerner (21%). System C, Dedalus and Allscripts Sunrise were also relatively common (13%, 10% and 7%, respectively). 70% of NHS Trusts with an EPR responded that they had a DSA; most of these use the National Early Warning Score (NEWS2). There was evidence that the EPR provider was related to the DSA algorithm. We found no evidence that Trusts were using EPRs to introduce data driven algorithms or DSAs able to include, for example, pre-existing conditions that may be known to increase risk.Not all Trusts were willing or able to provide details of their EPR or the underlying algorithm., Discussion: The majority of NHS Trusts use an EPR of some kind; many use a NEWS2-based DSA in keeping with national guidelines., Conclusion: Many English NHS Trusts use DSAs; even those using similar triggers vary and many recreate paper systems. Despite the proliferation of machine learning algorithms being developed to support early detection of sepsis, there is little evidence that these are being used to improve personalised sepsis detection., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objective: To assess implementation and ease of implementation of control measures in schools as reported by staff and parents., Design: A descriptive cross-sectional survey., Setting: Staff and parents/guardians of the 132 primary schools and 19 secondary schools participating in COVID-19 surveillance in school kids (sKIDs and sKIDsPLUS Studies)., Main Outcome Measure: Prevalence of control measures implemented in schools in autumn 2020, parental and staff perception of ease of implementation., Results: In total, 56 of 151 (37%) schools participated in this study, with 1953 parents and 986 staff members completing the questionnaire. Most common measures implemented by schools included regular hand cleaning for students (52 of 56, 93%) and staff (70 of 73, 96%), as reported by parents and staff, respectively, and was among the easiest to implement at all times for students (57%) and even more so, for staff (78%). Maintaining 2-metre distancing was less commonly reported for students (24%-51%) as it was for staff (81%-84%), but was one of the most difficult to follow at all times for students (25%) and staff (16%) alike. Some measures were more commonly reported by primary school compared to secondary school parents, including keeping students within the same small groups (28 of 41, 68% vs 8 of 15, 53%), ensuring the same teacher for classes (29 of 41, 71% vs 6 of 15, 40%). On the other hand, wearing a face covering while at school was reported by three-quarters of secondary school parents compared with only parents of 4 of 41 (10%) primary schools. Other measures such as student temperature checks (5%-13%) and advising staff work from home if otherwise healthy (7%-15%) were rarely reported., Conclusions: Variable implementation of infection control measures was reported, with some easier to implement (hand hygiene) than others (physical distancing)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Children and adolescents generally experience mild COVID-19. However, those with underlying physical health conditions are at a significantly increased risk of severe disease. Here, we present a comprehensive analysis of antibody and cellular responses in adolescents with severe neuro-disabilities who received COVID-19 vaccination with either ChAdOx1 (n=6) or an mRNA vaccine (mRNA-1273, n=8, BNT162b2, n=1). Strong immune responses were observed after vaccination and antibody levels and neutralisation titres were both higher after two doses. Both measures were also higher after mRNA vaccination and were further enhanced by prior natural infection where one vaccine dose was sufficient to generate peak antibody response. Robust T-cell responses were generated after dual vaccination and were also higher following mRNA vaccination. Early T-cells were characterised by a dominant effector-memory CD4+ T-cell population with a type-1 cytokine signature with additional production of IL-10. Antibody levels were well-maintained for at least 3 months after vaccination and 3 of 4 donors showed measurable neutralisation titres against the Omicron variant. T-cell responses also remained robust, with generation of a central/stem cell memory pool and showed strong reactivity against Omicron spike. These data demonstrate that COVID-19 vaccines display strong immunogenicity in adolescents and that dual vaccination, or single vaccination following prior infection, generate higher immune responses than seen after natural infection and develop activity against Omicron. Initial evidence suggests that mRNA vaccination elicits stronger immune responses than adenoviral delivery, although the latter is also higher than seen in adult populations. COVID-19 vaccines are therefore highly immunogenic in high-risk adolescents and dual vaccination might be able to provide relative protection against the Omicron variant that is currently globally dominant., Competing Interests: MR received funding for the COV-BOOST trial under contract via University Hospital Southampton NHS Foundation Trust, Funded by the UK NIHR/Vaccine Task Force (NIHR203292). Post-marketing surveillance reports on pneumococcal and meningococcal infection have been provided to vaccine manufacturers for which a cost recovery charge was made to GSK and Pfizer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dowell, Powell, Davis, Scott, Logan, Willett, Bruton, Ayodele, Jinks, Gunn, Spalkova, Sylla, Nicol, Zuo, Ireland, Okike, Baawuah, Beckmann, Ahmad, Garstang, Brent, Brent, White, Collins, Davis, Lim, Cohen, Kenny, Linley, Poh, Amirthalingam, Brown, Ramsay, Azad, Wright, Waiblinger, Moss and Ladhani.)

Seroepidemiological studies to monitor antibody kinetics are important for assessing the extent and spread of SARS-CoV-2 in a population. Noninvasive sampling methods are advantageous for reducing the need for venipuncture, which may be a barrier to investigations, particularly in pediatric populations. Oral fluids are obtained by gingiva-crevicular sampling from children and adults and are very well accepted. Enzyme immunoassays (EIAs) based on these samples have acceptable sensitivity and specificity compared to conventional serum-based antibody EIAs and are suitable for population-based surveillance. We describe the development and evaluation of SARS-CoV-2 IgG EIAs using SARS-CoV-2 viral nucleoprotein (NP) and spike (S) proteins in IgG isotype capture format and an indirect receptor-binding-domain (RBD) IgG EIA, intended for use in children as a primary endpoint. All three assays were assessed using a panel of 1,999 paired serum and oral fluids from children and adults participating in school SARS-CoV-2 surveillance studies during and after the first and second pandemic wave in the United Kingdom. The anti-NP IgG capture assay was the best candidate, with an overall sensitivity of 75% (95% confidence interval [CI]: 71 to 79%) and specificity of 99% (95% CI: 78 to 99%) compared with paired serum antibodies. Sensitivity observed in children (80%, 95% CI: 71 to 88%) was higher than that in adults (67%, CI: 60% to 74%). Oral fluid assays (OF) using spike protein and RBD antigens were also 99% specific and achieved reasonable but lower sensitivity in the target population (78%, 95% CI [68% to 86%] and 53%, 95% CI [43% to 64%], respectively). IMPORTANCE We report on the first large-scale assessment of the suitability of oral fluids for detection of SARS-CoV-2 antibody obtained from healthy children attending school. The sample type (gingiva-crevicular fluid, which is a transudate of blood but is not saliva) can be self collected. Although detection of antibodies in oral fluids is less sensitive than that in blood, our study suggests an optimal format for operational use. The laboratory methods we have developed can reliably measure antibodies in children, who are able to take their own samples. Our findings are of immediate practical relevance for use in large-scale seroprevalence studies designed to measure exposure to infection, as they typically require venipuncture. Overall, our data indicate that OF assays based on the detection of SARS-CoV-2 antibodies are a tool suitable for population-based seroepidemiology studies in children and highly acceptable in children and adults, as venipuncture is no longer necessary.

Background: Little is known about the risk of SARS-CoV-2 infection and transmission in educational settings. Public Health England initiated a study, COVID-19 Surveillance in School KIDs (sKIDs), in primary schools when they partially reopened from June 1, 2020, after the first national lockdown in England to estimate the incidence of symptomatic and asymptomatic SARS-CoV-2 infection, seroprevalence, and seroconversion in staff and students., Methods: sKIDs, an active, prospective, surveillance study, included two groups: the weekly swabbing group and the blood sampling group. The swabbing group underwent weekly nasal swabs for at least 4 weeks after partial school reopening during the summer half-term (June to mid-July, 2020). The blood sampling group additionally underwent blood sampling for serum SARS-CoV-2 antibodies to measure previous infection at the beginning (June 1-19, 2020) and end (July 3-23, 2020) of the summer half-term, and, after full reopening in September, 2020, and at the end of the autumn term (Nov 23-Dec 18, 2020). We tested for predictors of SARS-CoV-2 antibody positivity using logistic regression. We calculated antibody seroconversion rates for participants who were seronegative in the first round and were tested in at least two rounds., Findings: During the summer half-term, 11 966 participants (6727 students, 4628 staff, and 611 with unknown staff or student status) in 131 schools had 40 501 swabs taken. Weekly SARS-CoV-2 infection rates were 4·1 (one of 24 463; 95% CI 0·1-21·8) per 100 000 students and 12·5 (two of 16 038; 1·5-45·0) per 100 000 staff. At recruitment, in 45 schools, 91 (11·2%; 95% CI 7·9-15·1) of 816 students and 209 (15·1%; 11·9-18·9) of 1381 staff members were positive for SARS-CoV-2 antibodies, similar to local community seroprevalence. Seropositivity was not associated with school attendance during lockdown (p=0·13 for students and p=0·20 for staff) or staff contact with students (p=0·37). At the end of the summer half-term, 603 (73·9%) of 816 students and 1015 (73·5%) of 1381 staff members were still participating in the surveillance, and five (four students, one staff member) seroconverted. By December, 2020, 55 (5·1%; 95% CI 3·8-6·5) of 1085 participants who were seronegative at recruitment (in June, 2020) had seroconverted, including 19 (5·6%; 3·4-8·6) of 340 students and 36 (4·8%; 3·4-6·6) of 745 staff members (p=0·60)., Interpretation: In England, SARS-CoV-2 infection rates were low in primary schools following their partial and full reopening in June and September, 2020., Funding: UK Department of Health and Social Care., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

We conducted voluntary Covid-19 testing programmes for symptomatic and asymptomatic staff at a UK teaching hospital using naso-/oro-pharyngeal PCR testing and immunoassays for IgG antibodies. 1128/10,034 (11.2%) staff had evidence of Covid-19 at some time. Using questionnaire data provided on potential risk-factors, staff with a confirmed household contact were at greatest risk (adjusted odds ratio [aOR] 4.82 [95%CI 3.45-6.72]). Higher rates of Covid-19 were seen in staff working in Covid-19-facing areas (22.6% vs. 8.6% elsewhere) (aOR 2.47 [1.99-3.08]). Controlling for Covid-19-facing status, risks were heterogenous across the hospital, with higher rates in acute medicine (1.52 [1.07-2.16]) and sporadic outbreaks in areas with few or no Covid-19 patients. Covid-19 intensive care unit staff were relatively protected (0.44 [0.28-0.69]), likely by a bundle of PPE-related measures. Positive results were more likely in Black (1.66 [1.25-2.21]) and Asian (1.51 [1.28-1.77]) staff, independent of role or working location, and in porters and cleaners (2.06 [1.34-3.15])., Competing Interests: DE Lecture fees from Gilead, outside the submitted work, SL, DO, MC, ES, EL, FW, TJ, SC, AH, GD, SH, JK, KC, PF, JS, DV, FY, NS, PM, MD, TD, RS, LP, LD, AV, AA, BY, PD, AM, DS, FK, MN, MA, AB, NJ, LM, TC, BM, SH, RC, DC, DS, GS, TP, BH, AO, DE, CC, KJ, TW No competing interests declared, (© 2020, Eyre et al.)

Background: The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication., Methods: We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points., Results: Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of -1.4 percentage points (90% confidence interval [CI], -4.9 to 2.2; 95% CI, -5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P=0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%)., Conclusions: Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927 .).

Current guidelines recommend collection of multiple tissue samples for diagnosis of prosthetic joint infections (PJI). Sonication of explanted devices has been proposed as a potentially simpler alternative; however, reported microbiological yield varies. We evaluated sonication for diagnosis of PJI and other orthopedic device-related infections (DRI) at the Oxford Bone Infection Unit between October 2012 and August 2016. We compared the performance of paired tissue and sonication cultures against a "gold standard" of published clinical and composite clinical and microbiological definitions of infection. We analyzed explanted devices and a median of five tissue specimens from 505 procedures. Among clinically infected cases the sensitivity of tissue and sonication culture was 69% (95% confidence interval, 63 to 75) and 57% (50 to 63), respectively ( P < 0.0001). Tissue culture was more sensitive than sonication for both PJI and other DRI, irrespective of the infection definition used. Tissue culture yield was higher for all subgroups except less virulent infections, among which tissue and sonication culture yield were similar. The combined sensitivity of tissue and sonication culture was 76% (70 to 81) and increased with the number of tissue specimens obtained. Tissue culture specificity was 97% (94 to 99), compared with 94% (90 to 97) for sonication ( P = 0.052) and 93% (89 to 96) for the two methods combined. Tissue culture is more sensitive and may be more specific than sonication for diagnosis of orthopedic DRI in our setting. Variable methodology and case mix may explain reported differences between centers in the relative yield of tissue and sonication culture. Culture yield was highest for both methods combined., (Copyright © 2018 American Society for Microbiology.)

Childhood TB diagnosis is challenging. Studies in adults suggest Microscopic Observation Drug Susceptibility (MODS) culture or the Xpert MTB/RIF assay might be used to expand bacteriological diagnosis. However data from children are more limited. We prospectively compared MODS and Xpert MTB/RIF with standard microscopy and culture using the BD MGIT 960 system among 1442 Kenyan children with suspected TB. 97 specimens from 54 children were TB culture-positive: 91 (94%) by MGIT and 74 (76%) by MODS (p = 0.002). 72 (74%) culture-positive and 7 culture-negative specimens were Xpert MTB/RIF positive. Xpert MTB/RIF specificity was 100% (99.7-100%) among 1164 specimens from 892 children in whom TB was excluded, strongly suggesting all Xpert MTB/RIF positives are true positives. The sensitivity of MGIT, MODS and Xpert MTB/RIF was 88%, 71% and 76%, respectively, among all 104 true positive (culture and/or Xpert MTB/RIF positive) specimens. MGIT, MODS and Xpert MTB/RIF on the initial specimen identified 40/51 (78%), 33/51 (65%) and 33/51 (65%) culture-confirmed pulmonary TB cases, respectively; Xpert MTB/RIF detected 5 additional culture-negative cases. The high sensitivity and very high specificity of the Xpert MTB/RIF assay supports its inclusion in the reference standard for bacteriological diagnosis of childhood TB in research and clinical practice.

Culture of multiple periprosthetic tissue samples is the current gold standard for microbiological diagnosis of prosthetic joint infections (PJI). Additional diagnostic information may be obtained through culture of sonication fluid from explants. However, current techniques can have relatively low sensitivity, with prior antimicrobial therapy and infection by fastidious organisms influencing results. We assessed if metagenomic sequencing of total DNA extracts obtained direct from sonication fluid can provide an alternative rapid and sensitive tool for diagnosis of PJI. We compared metagenomic sequencing with standard aerobic and anaerobic culture in 97 sonication fluid samples from prosthetic joint and other orthopedic device infections. Reads from Illumina MiSeq sequencing were taxonomically classified using Kraken. Using 50 derivation samples, we determined optimal thresholds for the number and proportion of bacterial reads required to identify an infection and confirmed our findings in 47 independent validation samples. Compared to results from sonication fluid culture, the species-level sensitivity of metagenomic sequencing was 61/69 (88%; 95% confidence interval [CI], 77 to 94%; for derivation samples 35/38 [92%; 95% CI, 79 to 98%]; for validation samples, 26/31 [84%; 95% CI, 66 to 95%]), and genus-level sensitivity was 64/69 (93%; 95% CI, 84 to 98%). Species-level specificity, adjusting for plausible fastidious causes of infection, species found in concurrently obtained tissue samples, and prior antibiotics, was 85/97 (88%; 95% CI, 79 to 93%; for derivation samples, 43/50 [86%; 95% CI, 73 to 94%]; for validation samples, 42/47 [89%; 95% CI, 77 to 96%]). High levels of human DNA contamination were seen despite the use of laboratory methods to remove it. Rigorous laboratory good practice was required to minimize bacterial DNA contamination. We demonstrate that metagenomic sequencing can provide accurate diagnostic information in PJI. Our findings, combined with the increasing availability of portable, random-access sequencing technology, offer the potential to translate metagenomic sequencing into a rapid diagnostic tool in PJI., (Copyright © 2017 Street et al.)

Rapid MPT64-based immunochromatographic tests (MPT64 ICTs) have been developed to detect Mycobacterium tuberculosis complex (MTBC) in culture. We demonstrated the noninferiority of one commercial MTP64 ICT, the MGIT TBc identification (TBcID) test, to GenoType line probe assays for MTBC identification in positive MGIT cultures. Meta-analysis of MPT64 ICT performance for identification of MTBC in liquid culture confirmed similar very high sensitivities and specificities for all three commercial MPT64 assays for which sufficient data were available.