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Introduction: Low- and middle-income countries (LMICs) are disproportionally affected by conditions requiring emergency care but there are limited contextually appropriate studies performed within these settings involving the patient population and healthcare systems they aim to benefit. Over the past five years, researchers in the Western Cape of South Africa have produced approximately 20 % of all emergency care publications from Africa, yet no agreed list of research priorities exists. Establishing research priorities, via recognised consensus methods, can ensure that efforts and resources in LMICs are more appropriately targeted to the need., Method: Using a modified Delphi study, we invited a range of public and private representatives from different professional emergency care cadres within the Western Cape to identify current evidence gaps and consensus research priorities across the four areas of the WHO Emergency Care Systems framework: scene care, prehospital care, facility-based care, and the emergency care system itself. We then purposively selected eleven experts holding key academic and management positions to form a panel and perform a nominal group technique process to discuss these identified research priorities and establish a final list of priority research questions., Result: Forty of the sixty-six (61 %) emergency care professionals invited contributed to the Delphi phase of the study, with representation from all professional cadres. After deduplication, 154 research topics were identified in the first round. In the second round, 94 (61 %) topics were considered research priorities by at least 80 % of participants. Following the nominal group technique discussion, 26 questions were established as consensus research priorities having been ranked as a top ten priority by over 50 % of panellists., Conclusion: We were able to successfully collate expert opinion and identify existing emergency care knowledge gaps within the Western Cape province of South Africa. Key topics identified for future work included questions on current health-seeking behaviour, dispatch, interfacility transfer, and staff burnout., Competing Interests: At the time of peer review, Prof Lee Wallis was an editor of the African Journal of Emergency Medicine. Prof Wallis was not involved in the editorial workflow for this manuscript. The African Journal of Emergency Medicine applies a double blinded process for all manuscript peer reviews. The authors declared no further conflicts of interest., (© 2023 The Authors. Published by Elsevier B.V. on behalf of African Federation for Emergency Medicine.)

This Brief Report includes follow-up data about the sustainability and expansion of the Buprenorphine Team (B-Team), a hospital-based opioid treatment (HBOT) program. Between September 2018 and January 2023, the B-Team started 398 patients with opioid-use disorder (OUD) on buprenorphine therapy and coordinated outpatient care for 353 patients before discharge. Two-hundred and forty-nine of these patients were scheduled for follow-up at our partner addiction treatment clinic. Retention rates at our partner clinic remain relatively high: 73 patients (36% of eligible patients) continued to attend appointments between 6 and 12 months, and 40 of 180 patients (22%) who have been discharged from the hospital for at least 1 year continued to attend appointments. This model has been adopted at three additional Texas hospitals, resulting in rapid growth: 1037 patients were started on buprenorphine across these four sites during 2021-2022. Our longitudinal results support HBOT as an effective model for treating patients with OUD., (© 2023 Society of Hospital Medicine.)

Purpose. A study was undertaken to determine the risk factors and trends in antimicrobial resistance for enteric fever. Methodology. Demographic, antimicrobial susceptibility, typing and epidemiological data were examined for 2005-2012 in patients with enteric fever in London. Single and multivariable logistic regression was used to determine the risk factors associated with antibiotic resistance. Results. 453 cases with Salmonella enterica subsp. enterica serovar Paratyphi A, 17 with S . Paratyphi B and 611 with S. enterica subsp. enterica serovar Typhi were examined. For travellers, 335 (88 %) of S. Paratyphi A isolates were resistant to ciprofloxacin, but resistance to other antimicrobials was low. Almost 80 % (395) of the S . Typhi isolates were resistant to ciprofloxacin, 131 (26 %) to ampicillin, 131 (27 %) to chloramphenicol, 137 (28 %) to trimethoprim and 171 (28 %) to sulphonamide. None of the isolates were resistant to cephalosporins.A trend analysis for S . Typhi isolates showed no significant change in resistance to ampicillin, chloramphenicol, sulphonamide and trimethoprim or for multidrug resistance ( P =0.38). Overall resistance to ciprofloxacin increased for S . Paratyphi A ( P =0.018) and for S. Typhi ( P <0.001) but fell for S . Typhi in 2011-2012. Resistance profiles were reflected by specific phage types and countries visited by the travellers. Conclusions. The proportion of S . Typhi strains resistant to ampicillin, chloramphenicol and cotrimoxazole remained steady for the period 2005-2012. There was a significant increase in a trend for resistance to ciprofloxacin which increased until 2010, followed by a fall in 2011-2012. S. Paratyphi resistance to ciprofloxacin increased until 2012. Specific phage types were associated with resistance to specific antimicrobials and travel abroad.

The population of Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, exhibits limited DNA sequence variation, which complicates efforts to rationally discriminate individual isolates. Here we utilize data from whole-genome sequences (WGS) of nearly 2,000 isolates sourced from over 60 countries to generate a robust genotyping scheme that is phylogenetically informative and compatible with a range of assays. These data show that, with the exception of the rapidly disseminating H58 subclade (now designated genotype 4.3.1), the global S. Typhi population is highly structured and includes dozens of subclades that display geographical restriction. The genotyping approach presented here can be used to interrogate local S. Typhi populations and help identify recent introductions of S. Typhi into new or previously endemic locations, providing information on their likely geographical source. This approach can be used to classify clinical isolates and provides a universal framework for further experimental investigations.

Whole-genome sequencing (WGS) was carried out on 87 isolates of sequence type 111 (ST-111) of Pseudomonas aeruginosa collected between 2005 and 2014 from 65 patients and 12 environmental isolates from 24 hospital laboratories across the United Kingdom on an Illumina HiSeq instrument. Most isolates (73) carried VIM-2, but others carried IMP-1 or IMP-13 (5) or NDM-1 (1); one isolate had VIM-2 and IMP-18, and 7 carried no metallo-beta-lactamase (MBL) gene. Single nucleotide polymorphism analysis divided the isolates into distinct clusters; the NDM-1 isolate was an outlier, and the IMP isolates and 6/7 MBL-negative isolates clustered separately from the main set of 73 VIM-2 isolates. Within the VIM-2 set, there were at least 3 distinct clusters, including a tightly clustered set of isolates from 3 hospital laboratories consistent with an outbreak from a single introduction that was quickly brought under control and a much broader set dominated by isolates from a long-running outbreak in a London hospital likely seeded from an environmental source, requiring different control measures; isolates from 7 other hospital laboratories in London and southeast England were also included. Bayesian evolutionary analysis indicated that all the isolates shared a common ancestor dating back ∼50 years (1960s), with the main VIM-2 set separating approximately 20 to 30 years ago. Accessory gene profiling revealed blocks of genes associated with particular clusters, with some having high similarity (≥95%) to bacteriophage genes. WGS of widely found international lineages such as ST-111 provides the necessary resolution to inform epidemiological investigations and intervention policies., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Background: The study sought evidence for changes in the proportions of antibiotic resistant strains among isolates of Salmonella enterica serovar Typhi (S. typhi) and Salmonella enterica serovar Paratyphi (S. paratyphi) between 2005 and 2012., Methods: Blood culture isolates of S. typhi and S. paratyphi from patients attending Newham and The Royal London Hospitals were included in the study. The organisms were cultured on selective media and identified by Maldi-ToF, API 20E and serology. Minimum inhibitory concentrations (MICs) of augmentin, chloramphenicol, co-trimoxazole, ceftriaxone, ciprofloxacin and azithromycin were determined by E tests for 194 isolates., Results: Median MICs of ciprofloxacin and ceftriaxone were stable at 0.5 mg/L and 0.125 mg/L, respectively. Chloramphenicol, azithromycin, co-trimoxazole and augmentin median MICs were 4 mg/L, 8 mg/L, 0.064 mg/L and 0.5 mg/L, respectively. MIC90 values were lower than the resistant breakpoint for ceftriaxone, azithromycin and augmentin, but were >256 mg/L for chloramphenicol, 32 mg/L for co-trimoxazole and 1 mg/L for ciprofloxacin., Conclusions: Antibiotic resistance remained stable for enteric fever isolates between 2005 and 2012. The isolates remained susceptible to augmentin, ceftriaxone and azithromycin over this period, but the MIC90 was greater than the resistant breakpoint for chloramphenicol, cotrimoxazole and ciprofloxacin. The implications for clinical practice are that isolates of S. typhi and S. paratyphi from East London remain sensitive to ceftriaxone and azithromycin., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Notwithstanding that 'public engagement' is conceptualised differently internationally and in different academic disciplines, higher education institutions largely accept the importance of public engagement with research. However, there is limited evidence on how researchers conceptualise engagement, their views on what constitutes engagement and the communities they would (or would not) like to engage with. This paper presents the results of a survey of researchers in the Open University that sought to gather data to fill these gaps. This research was part of an action research project designed to embed engagement in the routine practices of researchers at all levels. The findings indicate that researchers have a relatively narrow view of public engagement with research and the communities with which they interact. It also identified that very few strategically evaluate their public engagement activities. We conclude by discussing some of the interventions we have introduced with the aim of broadening and deepening future researcher engagement.

Purpose: The clinical presentation and epidemiology for patients with enteric fever at two hospitals in East London during 2007-2012 is described with the aim to identify preventive opportunities and to reduce the cost of treatment., Methods: A retrospective analysis of case notes from patients admitted with enteric fever during 2007 to 2012 with a microbiologically confirmed diagnosis was undertaken. Details on clinical presentation, travel history, demographic data, laboratory parameters, treatment, patient outcome and vaccination status were collected., Results: Clinical case notes were available for 98/129 (76%) patients including 69 Salmonella enterica serovar Typhi (S. Typhi) and 29 Salmonella enterica serovar Paratyphi (S. Paratyphi). Thirty-four patients (35%) were discharged from emergency medicine without a diagnosis of enteric fever and then readmitted after positive blood cultures. Seventy-one of the 98 patients (72%) were UK residents who had travelled abroad, 23 (23%) were foreign visitors/new entrants to the UK and four (4%) had not travelled abroad. Enteric fever was not considered in the initial differential diagnosis for 48/98 (49%) cases. The median length of hospital stay was 7 days (range 0-57 days). The total cost of bed days for managing enteric fever was £454,000 in the two hospitals (mean £75,666/year). Median time to clinical resolution was five days (range 1-20). Seven of 98 (7%) patients were readmitted with relapsed or continued infection. Six of the 71 (8%) patients had received typhoid vaccination, 34 (48%) patients had not received vaccination, and for 31 cases (44%) vaccination status was unknown., Conclusions: Further interventions regarding education and vaccination of travellers and recognition of the condition by emergency medicine clinicians in travellers to South Asia is required.

Aim: To examine performance in the UK National External Quality Assessment Scheme (UKNEQAS) for toxoplasma serology for evidence of discrepant results as compared with the predistribution and postdistribution results supplied by the toxoplasma reference laboratories., Methods: Analysis of performance in the toxoplasma IgG and IgM schemes was made for the period 1994-2008 to look for trends in performance., Results: For the IgG scheme, a mean of 98% of participants obtained the correct result for detection of toxoplasma-specific antibody. The most common problem was failure to detect low levels of antibody. In some cases this was the result of participants deviating from the manufacturer's instructions and using higher cut-off levels. For the IgM scheme, an average of 95% of participants obtained the correct result for toxoplasma antibody detection. The most common problem was the failure of some enzyme immunoassay kits to detect specific toxoplasma IgM antibody, which was detected by the more sensitive immunosorbent agglutination assay., Conclusions: Performance standards in the UKNEQAS toxoplasma serology schemes were high. The problems encountered have highlighted the importance of detecting low levels of antibody, adhering to the kit manufacturer's instructions and selecting an appropriate assay for the clinical situation.

Clostridium difficile can be a fatal hospital-acquired infection and its prevalence has increased. Accurate diagnosis of C difficile is essential for patient management, infection control, and for defining its epidemiology. We did a systematic review of commonly used commercial assays for detection of C difficile toxin (CDT) A and B in stool samples. By comparison of detection of CDT in cell culture with or without selective culture for C difficile, the median sensitivities and specificities (IQR) were as follows: Meridian Premier 0.95 (0.86-0.97) and 0.97 (0.95-0.98), TechLab Tox A/B II 0.83 (0.82-0.85) and 0.99 (0.98-1.00), TechLab Tox A/B Quik Chek 0.84 (0.81-0.87) and 1.00 (0.99-1.00), Remel Xpect 0.82 (0.75-0.89) and 0.96 (0.95-0.98), Meridian Immunocard 0.90 (0.84-0.92) and 0.99 (0.98-1.00), and BioMérieux VIDAS 0.76 and 0.93. If the prevalence of CDT A and B in stool samples is relatively low (<10%), the positive predictive value of these assays is unacceptably low (eg, <50% in some circumstances) and will vary depending on the assay and number of samples tested. This low positive predictive value impinges on clinical management, outbreaks, and makes epidemiological data unreliable. To improve diagnosis, we suggest a two-stage testing strategy for C difficile toxin with an initial highly sensitive rapid screening test to identify positive samples that are then confirmed by a reference method.

Background: Pulmonary decline accelerates in cystic fibrosis-related diabetes (CFRD) proportional to severity of glucose intolerance, but mechanisms are unclear. In people without CF, airway glucose (AG) concentrations are elevated when blood glucose (BG)> or =8 mmol L(-1) (airway threshold), and are associated with acquisition of respiratory infection., Methods: To determine the relationship between BG and AG, 40 CF patients underwent paired BG and AG (nasal) measurements. Daily time with BG>airway threshold was compared in 10 CFRD, 10 CF patients with normal glucose tolerance (CF-NGT) and 10 healthy volunteers by continuous BG monitoring. The effect of glucose at airway concentrations on bacterial growth was determined in vitro by optical densitometry., Results: AG was present more frequently (85%-vs.-19%, p<0.0001) and at higher concentrations (0.5-3 mmol L(-1)-vs.-0.5-1 mmol L(-1), p<0.0001) when BG was > or =8 mmol L(-1)-vs.-<8 mmol L(-1). Daily time with BG> or =8 mmol L(-1) was CFRD (49+/-25%), CF-NGT (6+/-5%), healthy volunteers (1+/-3%), p<0.0001. Staphylococcus aureus growth increased at > or =0.5 mmol L(-1) (p=0.006) and Pseudomonas aeruginosa growth above 1-4 mmol L(-1) glucose (p=0.039)., Conclusions: BG> or =8 mmol L(-1) predicted elevated AG concentrations in CF, at least in nasal secretions. CFRD patients spent approximately 50% day with BG>airway threshold, implying persistently elevated AG concentrations. Further studies are required to determine whether elevated airway glucose concentrations contribute to accelerated pulmonary decline in CFRD.

Background: The risk of nosocomial infection is increased in critically ill patients by stress hyperglycaemia. Glucose is not normally detectable in airway secretions but appears as blood glucose levels exceed 6.7-9.7 mmol/l. We hypothesise that the presence of glucose in airway secretions in these patients predisposes to respiratory infection., Methods: An association between glucose in bronchial aspirates and nosocomial respiratory infection was examined in 98 critically ill patients. Patients were included if they were expected to require ventilation for more than 48 hours. Bronchial aspirates were analysed for glucose and sent twice weekly for microbiological analysis and whenever an infection was suspected., Results: Glucose was detected in bronchial aspirates of 58 of the 98 patients. These patients were more likely to have pathogenic bacteria than patients without glucose detected in bronchial aspirates (relative risk 2.4 (95% CI 1.5 to 3.8)). Patients with glucose were much more likely to have methicillin resistant Staphylococcus aureus (MRSA) than those without glucose in bronchial aspirates (relative risk 2.1 (95% CI 1.2 to 3.8)). Patients who became colonised or infected with MRSA had more infiltrates on their chest radiograph (p<0.001), an increased C reactive protein level (p<0.05), and a longer stay in the intensive care unit (p<0.01). Length of stay did not determine which patients acquired MRSA., Conclusion: The results imply a relationship between the presence of glucose in the airway and a risk of colonisation or infection with pathogenic bacteria including MRSA.

Background: Animal experiments have shown that antibodies against capsular polysaccharide enhance phagocytosis of pneumococcal bacteria and that antibodies against pneumolysin are anti-inflammatory and prevent pneumococcal invasion. It is not known if an antibody response to pneumolysin can be acquired from natural exposure to pneumococcal bacteria or how the concentration of pneumolysin antibody at the mucosal surface compares with that of antibodies against pneumococcal capsular polysaccharide. This study used an equal potency method to measure specific antibody concentrations against pneumolysin and pneumococcal capsular polysaccharides in order to facilitate comparative estimates of concentrations in saliva and serum. The results may provide experimental information as a basis for an improved pneumococcal vaccine strategy., Results: Healthy individuals had higher IgM and IgG antibody concentrations against capsular polysaccharide than against pneumolysin in both saliva and serum, but for IgA the converse was true. Patients with acute pneumococcal infection had significantly lower concentrations of specific IgG antibodies against both antigens than the healthy group. These patients also had significantly higher concentrations of IgM antibody against both antigens than the healthy control group., Discussion: Healthy individuals acquire a comparatively lower concentration of antibody to pneumolysin than to pneumococcal capsular polysaccharides from natural exposure to pneumococcal bacteria. Patients infected by pneumococcal bacteria have lower specific IgG antibody concentrations to both antigens than healthy individuals. These findings support the view that pneumolysin could potentially be used as a vaccine. For enhanced effectiveness, it could be used as a supplement to Pneumovax((R))II rather than as a replacement. The two acquired antibodies, i.e. to pneumolysin and to capsular polysaccharide, could then play their protective roles at different stages in the course of pneumococcal infection, and together contribute to an effective immune defence against Streptococcus pneumoniae.

In a study involving 14 laboratories supported by the European Community Biomed 2 program, we evaluated immunologic methods for the postnatal diagnosis of congenital toxoplasmosis (CT). Among babies born to mothers who seroconverted to positivity for toxoplasmosis during pregnancy, we analyzed 55 babies with CT on the basis of persistent anti-Toxoplasma immunoglobulin G (IgG) at 1 year of life and 50 control babies without anti-Toxoplasma IgG at 1 year of life in the absence of curative treatment with pyrimethamine-sulfonamides. We tested in-house methods such as the enzyme-linked immunofiltration assay (ELIFA) or Immunoblotting (IB) for the detection of IgG or IgM; these methods allowed comparison of the immunologic profiles of the mothers and the infants. We compared ELIFA and IB with a commercial enzyme immunoassay (EIA) or in-house immunosorbent agglutination assay (ISAGA) for the detection of IgM or IgA. The performances of combinations of methods were also assessed. A cumulative sensitivity of 98% during a 1-year follow-up was obtained with the ELIFA plus ISAGA combination. Only one case of CT was missed by the ELIFA plus ISAGA combination, whereas three cases were missed by the IB plus ISAGA combination, even though 48% of patients with CT were treated with pyrimethamine-sulfonamides, which are known to inhibit antibody neosynthesis. A similar performance was obtained with either ELIFA or IB in combination with EIA. The difference in performance between ELIFA plus ISAGA and IB plus ISAGA was not statistically significant (P = 0.31), and we conclude that both combinations of tests can be used for the diagnosis of CT in newborns.

The dye test for the detection of Toxoplasma-specific antibodies was first described by Sabin and Feldman 50 years ago. The test is highly specific and sensitive and considerable information is available on the development and persistence of dye test antibodies after primary Toxoplasma infection. However, the test uses live Toxoplasma gondii and is now only employed in a few laboratories. It is still the reference method for the serodiagnosis of toxoplasmosis, and a multicentre study comparing dye test results between different laboratories was much needed. We report in this article the results of a multicentre evaluation of the test involving nineteen laboratories in eight countries. The study revealed overall satisfactory standardization between the laboratories, but there were differences in the test protocols, the use of reference/standard preparations and the interpretation of results. There is still no agreement on the level of dye test values which reflect infection with the parasite, and conversion from titres to international units (IUs) did not improve standardization. However, the results indicated that a value of > 4 IU or a titre of 1:16 met the definition of positivity of most participants. We recommend that the dye test be retained as a reference method and that interlaboratory standardization be improved by the use of a common protocol and the expression of results in titres.

Cardiac biopsy samples taken from transplant recipients around the time of primary toxoplasma infection were investigated by conventional histology and amplification of the P30 gene of Toxoplasma gondii by the polymerase chain reaction (PCR). Toxoplasma was detected more frequently by PCR than histology which may reflect the enhanced sensitivity of the former technique. Further studies are required to determine the optimal amount of tissue which should be examined by each technique and to develop a PCR assay capable of distinguishing between quiescent infection and active toxoplasmosis.

Sera from 94 patients infected with human immunodeficiency virus (HIV) 1, together with 86 controls, attending the Kenyatta National Hospital, Nairobi were examined for antibodies to Toxoplasma gondii using enzyme immunoassay and latex and dye tests. 54% had Toxoplasma-specific immunoglobulin G (IgG) by dye test. 22% of the HIV-positive group had IgG levels in excess of 180 units/ml (approximating to a dye test titre of 1:1300) compared to 1% of the HIV-negative group. There was no correlation between high levels of IgG and clinical stage of HIV disease or features indicative of active toxoplasmosis. It is proposed that the elevated serum IgG is a reflection of early Toxoplasma reactivation, not necessarily associated with disease.

In the USA and Europe, toxoplasmosis is well recognized as an important cause of morbidity and mortality among immunocompromised individuals. Toxoplasma gondii has been shown to be a common opportunistic infection in patients infected with the human immunodeficiency virus (HIV) in the USA and Europe with published estimates ranging from 20% to 80%. The importance of Toxoplasma infection in East Africa has not yet been defined. The seroprevalence rates of toxoplasmosis in Zambian and Ugandan patients were determined using the dye test (DT) and the latex agglutination test (LAT). The geographical variation in seroprevalence rates noted in western countries was also found in these African countries, with Zambia showing significantly lower rates than Uganda. 34% of Ugandan (64/186) and 4% of Zambian (8/187) patients infected with HIV, compared with 27% of Ugandan (26/93) and 11% of Zambian (20/189) HIV-negative persons, had anti-Toxoplasma immunoglobulin G antibodies. With the LAT, 13% of the Ugandan and 7% of the Zambian sera gave a false positive result. The relevance of Toxoplasma serology in Africa is discussed.

A controlled, prospective trial was conducted on an orthopaedic ward to test the use of peroxide disinfection of drainage bags as the only measure taken to affect the rate of hospital-acquired, catheter-associated urinary tract infection (UTI). A significant reduction (P less than 0.05) in the number of patients with catheter-associated UTI occurred with the use of bag disinfectant when compared with patients in whom this technique was not used. We consider this technique to be suitable for the management of catheterised patients on general hospital wards to reduce catheter-associated UTI and environmental spread of their bacteria.

We report a case of endocarditis associated with a highly gentamicin-resistant enterococcus that failed to respond to conventional antibiotic combination therapy. Clinical resolution was achieved following cardiac surgery and antimicrobial treatment dictated by in vitro testing of the patient's organism. Laboratories should test blood culture isolates of enterococci for high level gentamicin resistance. Management of such cases requires individual assessment and extensive laboratory investigation.