An exploration of the political, social, economic and cultural factors affecting how different global regions initially reacted to the COVID-19 pandemic.

Responses to the early (February-July 2020) COVID-19 pandemic varied widely, globally. Reasons for this are multiple but likely relate to the healthcare and financial resources then available, and the degree of trust in, and economic support provided by, national governments. Cultural factors also affected how different populations reacted to the various pandemic restrictions, like masking, social distancing and self-isolation or self-quarantine. The degree of compliance with these measures depended on how much individuals valued their needs and liberties over those of their society. Thus, several themes may be relevant when comparing pandemic responses across different regions. East and Southeast Asian populations tended to be more collectivist and self-sacrificing, responding quickly to early signs of the pandemic and readily complied with most restrictions to control its spread. Australasian, Eastern European, Scandinavian, some Middle Eastern, African and South American countries also responded promptly by imposing restrictions of varying severity, due to concerns for their wider society, including for some, the fragility of their healthcare systems. Western European and North American countries, with well-resourced healthcare systems, initially reacted more slowly, partly in an effort to maintain their economies but also to delay imposing pandemic restrictions that limited the personal freedoms of their citizens.

Screening for Candida auris in patients admitted to eight intensive care units in England, 2017 to 2018.

BackgroundCandida auris is an emerging multidrug-resistant fungal pathogen associated with bloodstream, wound and other infections, especially in critically ill patients. C. auris carriage is persistent and is difficult to eradicate from the hospital environment.AimWe aimed to pilot admission screening for C. auris in intensive care units (ICUs) in England to estimate prevalence in the ICU population and to inform public health guidance.MethodsBetween May 2017 and April 2018, we screened admissions to eight adult ICUs in hospitals with no previous cases of C. auris, in three major cities. Swabs were taken from the nose, throat, axilla, groin, perineum, rectum and catheter urine, then cultured and identified using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). Patient records were linked to routine ICU data to describe and compare the demographic and health indicators of the screened cohort with a national cohort of ICU patients admitted between 2016 and 2017.ResultsAll C. auris screens for 921 adults from 998 admissions were negative. The upper confidence limit of the pooled prevalence across all sites was 0.4%. Comparison of the screened cohort with the national cohort showed it was broadly similar to the national cohort with respect to demographics and co-morbidities.ConclusionThese findings imply that C. auris colonisation among patients admitted to ICUs in England is currently rare. We would not currently recommend widespread screening for C. auris in ICUs in England. Hospitals should continue to screen high-risk individuals based on local risk assessment.

Drivers of Broad-Spectrum Antibiotic Overuse across Diverse Hospital Contexts-A Qualitative Study of Prescribers in the UK, Sri Lanka and South Africa.

Antimicrobial stewardship programs focus on reducing overuse of broad-spectrum antibiotics (BSAs), primarily through interventions to change prescribing behavior. This study aims to identify multi-level influences on BSA overuse across diverse high and low income, and public and private, healthcare contexts. Semi-structured interviews were conducted with 46 prescribers from hospitals in the UK, Sri Lanka, and South Africa, including public and private providers. Interviews explored decision making about prescribing BSAs, drivers of the use of BSAs, and benefits of BSAs to various stakeholders, and were analyzed using a constant comparative approach. Analysis identified drivers of BSA overuse at the individual, social and structural levels. Structural drivers of overuse varied significantly across contexts and included: system-level factors generating tensions with stewardship goals; limited material resources within hospitals; and patient poverty, lack of infrastructure and resources in local communities. Antimicrobial stewardship needs to encompass efforts to reduce the reliance on BSAs as a solution to context-specific structural conditions.

Moral and Contextual Dimensions of "Inappropriate" Antibiotic Prescribing in Secondary Care: A Three-Country Interview Study.

Overuse of broad-spectrum antibiotics in secondary care is a key contributor to the emergence and spread of antimicrobial resistance (AMR); efforts are focused on minimizing antibiotic overuse as a crucial step toward containing the global threat of AMR. The concept of overtreatment has, however, been difficult to define. Efforts to address the overuse of medicine need to be informed by an understanding of how prescribers themselves understand the problem. We report findings from a qualitative interview study of 46 acute care hospital prescribers differing in seniority from three countries: United Kingdom, Sri Lanka and South Africa. Prescribers were asked about their understanding of inappropriate use of antibiotics. Prescriber definitions of inappropriate use included relatively clear-cut and unambiguous cases of antibiotics being used "incorrectly" (e.g., in the case of viral infections). In many cases, however, antibiotic prescribing decisions were seen as involving uncertainty, with prescribers having to make decisions about the threshold for appropriate use. Decisions about thresholds were commonly framed in moral terms. Some prescribers drew on arguments about their duty to protect public health through having a high threshold for prescribing, while others made strong arguments for prioritizing risk avoidance for the patients in front of them, even at a cost of increased resistance. Notions of whether prescribing was inappropriate were also contextually dependent: high levels of antibiotic prescribing could be seen as a rational response when prescribers were working in challenging contexts, and could be justified in relation to financial and social considerations. Inappropriate antibiotic use is framed by prescribers not just in clinical, but also in moral and contextual terms; this has implications for the design and implementation of antibiotic stewardship interventions aiming to reduce inappropriate use of antibiotics globally.

Face mask sampling for the detection of Mycobacterium tuberculosis in expelled aerosols.

BACKGROUND: Although tuberculosis is transmitted by the airborne route, direct information on the natural output of bacilli into air by source cases is very limited. We sought to address this through sampling of expelled aerosols in face masks that were subsequently analyzed for mycobacterial contamination. METHODS: In series 1, 17 smear microscopy positive patients wore standard surgical face masks once or twice for periods between 10 minutes and 5 hours; mycobacterial contamination was detected using a bacteriophage assay. In series 2, 19 patients with suspected tuberculosis were studied in Leicester UK and 10 patients with at least one positive smear were studied in The Gambia. These subjects wore one FFP30 mask modified to contain a gelatin filter for one hour; this was subsequently analyzed by the Xpert MTB/RIF system. RESULTS: In series 1, the bacteriophage assay detected live mycobacteria in 11/17 patients with wearing times between 10 and 120 minutes. Variation was seen in mask positivity and the level of contamination detected in multiple samples from the same patient. Two patients had non-tuberculous mycobacterial infections. In series 2, 13/20 patients with pulmonary tuberculosis produced positive masks and 0/9 patients with extrapulmonary or non-tuberculous diagnoses were mask positive. Overall, 65% of patients with confirmed pulmonary mycobacterial infection gave positive masks and this included 3/6 patients who received diagnostic bronchoalveolar lavages. CONCLUSION: Mask sampling provides a simple means of assessing mycobacterial output in non-sputum expectorant. The approach shows potential for application to the study of airborne transmission and to diagnosis.

Randomised controlled trial and health economic evaluation of the impact of diagnostic testing for influenza, respiratory syncytial virus and Streptococcus pneumoniae infection on the management of acute admissions in the elderly and high-risk 18- to 64-year-olds.

BACKGROUND: Western industrialised nations face a large increase in the number of older people. People over the age of 60 years account for almost half of the 16.8 million hospital admissions in England from 2009 to 2010. During 2009-10, respiratory infections accounted for approximately 1 in 30 hospital admissions and 1 in 20 of the 51.5 million bed-days. OBJECTIVE: To determine the diagnostic accuracy and clinical effectiveness and cost-effectiveness of rapid molecular and near-patient diagnostic tests for influenza, respiratory syncytial virus (RSV) and Streptococcus pneumoniae infections in comparison with traditional laboratory culture. METHODS: We carried out a randomised controlled trial (RCT) to evaluate impact on prescribing and clinical outcomes of point-of-care tests (POCTs) for influenza A and B and pneumococcal infection, reverse transcriptase-polymerase chain reaction (RT-PCR) tests for influenza A and B and RSV A and B, and conventional culture for these pathogens. We evaluated diagnostic accuracy of POCTs for influenza and pneumococcal infection, RT-PCR for influenza and sputum culture for S. pneumoniae using samples collected during the RCT. We did a systematic review and meta-analysis of POCTs for influenza A and B. We evaluated ease and speed of use of each test, process outcomes and cost-effectiveness. RESULTS: There was no evidence of association between diagnostic group and prescribing or clinical outcomes. Using PCR as 'gold standard', Quidel Influenza A + B POCT detected 24.4% [95% confidence interval (CI) 16.0% to 34.6%] of influenza infections (specificity 99.7%, 95% CI 99.2% to 99.9%); viral culture detected 21.6% (95% CI 13.5% to 31.6%; specificity 99.8%, 95% CI 99.4% to 100%). Using blood culture as 'gold standard', BinaxNOW pneumococcal POCT detected 57.1% (95% CI 18.4% to 90.1%) of pneumococcal infections (specificity 92.5%; 95% CI 90.6% to 94.1%); sputum culture detected 100% (95% CI 2.5% to 100%; specificity 97.2%, 95% CI 94.3% to 98.9%). Overall, pooled estimates of sensitivity and specificity of POCTs for influenza from the literature were 74% (95% CI 67% to 80%) and 99% (95% CI 98% to 99%), respectively. Median intervals from specimen collection to test result were 15 minutes [interquartile range (IQR) 10-23 minutes) for Quidel Influenza A + B POCT, 20 minutes (IQR 15-30 minutes) for BinaxNOW pneumococcal POCT, 50.8 hours (IQR 44.3-92.6 hours) for semi-nested conventional PCR, 29.2 hours (IQR 26-46.9 hours) for real-time PCR, 629.6 hours (IQR 262.5-846.7 hours) for culture of influenza and 84.4 hours (IQR 70.7-137.8 hours) and 71.4 hours (IQR 69.15-84.0 hours) for culture of S. pneumoniae in blood and sputum, respectively. Both POCTs were rated straightforward and undemanding; blood culture was moderately complex and all other tests were complex. Costs and quality-adjusted life-years (QALYs) of each diagnostic strategy were similar. Incrementally, PCR was most cost-effective (78.3% probability at a willingness to pay of £20,000/QALY). Few patients were admitted within a timescale conducive to treatment with a neuraminidase inhibitor according to National Institute for Health and Care Excellence guidance. LIMITATIONS: The accuracy study was limited by inadequate gold standards. CONCLUSIONS: All tests had limitations. We found no evidence that POCTs for influenza or S. pneumoniae, or PCR for influenza or RSV influenced antimicrobial prescribing or clinical outcomes. The total costs and QALYs of each diagnostic strategy were similar, although, incrementally, PCR was the most cost-effective strategy. The analysis does not support routine use of POCTs for either influenza or pneumococcal antigen for adults presenting with acute cardiopulmonary conditions, but suggests that conventional viral culture for clinical diagnosis should be replaced by PCR. TRIAL REGISTRATION: Current Controlled Trials ISRCTN21521552. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 36. See the NIHR Journals Library website for further project information.

A two-tube combined TaqMan/SYBR Green assay to identify mycobacteria and detect single global lineage-defining polymorphisms in Mycobacterium tuberculosis.

We have developed a novel real-time PCR assay to identify and perform preliminary genotyping of mycobacteria in a manner tailored to our local service. Within a single thermocycler run, mycobacterial 16S rDNA and the Mycobacterium tuberculosis global lineage-defining RD750 polymorphism are targeted in separate reaction tubes, each of which includes both TaqMan and SYBR Green chemistries. The results of this 16S-RD assay differentiate M. tuberculosis complex (MTBC) from nontuberculous mycobacteria (NTM) and recognize whether or not MTBC isolates belong to the East African-Indian lineage, the single most frequently isolated global MTBC lineage in our service. If required, NTM amplicons may be sequenced to provide more specific identities. We report the technical performance of this assay on 88 mycobacteria-positive cultures and discuss its use in the initial management of mycobacterial infections. The 16S-RD assay correctly identified all 70 MTBC-positive cultures and 17 NTM-positive cultures while contemporaneously recognizing 26 MTBC isolates as within and 44 outside the East African-Indian lineage. In artificial samples, the combined assay also showed limited potential to detect mixed mycobacterial infections (MTBC/NTM) and tuberculosis infections involving more than one global MTBC lineage. The approach we have established can be readily tailored to targets of particular value for any mycobacterial diagnostic service, thereby optimizing the value of the results for local clinical and public health management of mycobacterial infections.

Enteric fever in a UK regional infectious diseases unit: a 10 year retrospective review.

INTRODUCTION: Enteric fever is an increasingly common diagnosis in returning travellers in the UK. METHODS: We performed a retrospective descriptive study of culture-confirmed cases of enteric fever admitted to University Hospitals Leicester, UK between January 1999 and April 2009. RESULTS: 100 cases of enteric fever were identified in adults (n = 76) and children (n = 24). The median age of adult subjects was 38 (range 18-71) and 55% were male. Of the 61 adult cases with notes available, 60 (98.3%) were of Asian ethnicity and 56 (92%) had a recent travel history, principally to the Indian Subcontinent. Symptoms included fever (100%), headache (62%), diarrhoea (59%) and abdominal pain (44%). Common examination findings included pyrexia and mild generalized abdominal tenderness. Mild hyponatraemia, transaminitis and a normal white cell count were commonly identified. Reduced ciprofloxacin sensitivity was common and increased over the study period. Median fever clearance time was 6 days, and treatment failure occurred in 20% of cases. Relapse occurred in 2 patients. Complications were unusual, and one patient died. DISCUSSION: Patients with enteric fever presented with a non-specific febrile illness within one month after returning from travel, and most had an uncomplicated clinical course. Increasing ciprofloxacin insensitivity was the likely explanation for a high treatment failure rate and this agent can no longer recommended as empirical treatment.

Olecranon bursitis secondary to Mycobacterium kansasii infection in a patient receiving infliximab for Behcet's disease.

We present a case of Mycobacterium kansasii olecranon bursitis in a woman with known immunosuppression secondary to the treatment received for her Behçet's disease. We found only one other case report of olecranon bursitis caused by M. kansasii in the literature, which, unlike our case, presented in an immunocompetent adult following trauma. This case extends the range of opportunistic mycobacterial infections that are associated with anti-tumour necrosis factor therapy.

Unusual findings and diagnostic challenges in a child with Lemierre's disease.

16S rDNA polymerase chain reaction (PCR) in the diagnosis of fastidious organisms is becoming increasingly commonplace. We present the case of a child admitted to an acute paediatric unit of a university teaching hospital with otorrhoea, torticollis, and cervical lymphadenopathy. Examination revealed hepatosplenomegaly associated with pancytopenia. Radiological imaging confirmed a retropharyngeal abscess, bilateral mastoiditis, cerebellar lesions, and venous sinus thrombosis. Swabs of aural discharge grew anaerobes. Drainage of the retropharyngeal abscess and bilateral mastoidectomy were performed. Bone marrow aspiration was initially suspicious of acute leukaemia prompting further investigations, but cytogenetic analysis ruled out this diagnosis and changes were attributed to severe sepsis. Following 27 days of intravenous antibiotics and after clinical improvement, clindamycin was started. Intraoperative pus yielded no significant pathogens. A 16S rDNA PCR confirmed Fusobacterium necrophorum. The boy was discharged on a 6 week course of oral clindamycin.

Identification of Neisseria gonorrhoeae as the causative agent in a case of culture-negative dermatitis-arthritis syndrome using real-time PCR.

Sexually transmitted infections (STIs) are an increasingly common and important cause of a fever in a returning traveler. Systemic complications of STIs, human immunodeficiency virus seroconversion illness, and secondary syphilis are diagnoses that can easily be missed. We present a case of culture-negative disseminated gonococcal infection presenting with fever, malaise, polyarthralgia, arthritis, and a rash that developed following orogenital contact and was diagnosed using real-time polymerase chain reaction. This technology has major potential to improve the speed and sensitivity of diagnosis and consequent management of patients with this syndrome.

Identification of Streptococcus gallolyticus subsp. macedonicus as the etiological agent in a case of culture-negative multivalve infective endocarditis by 16S rDNA PCR analysis of resected valvular tissue.

Today, PCR using broad-range primers is being used increasingly to detect pathogens from resected heart valves. Herein is described the first case of multivalve infective endocarditis where 16S rDNA PCR was used to detect a single pathogen from two affected valves in a 61-year-old man. Triple heart valve replacement was required despite six weeks of appropriate antimicrobial therapy. The organism was confirmed as Streptococcus gallolyticus subsp. macedonicus, a member of the 'S. equinus/S. bovis' complex. To date, only one report has been made of human infection due to this organism. This may be due to the limited resolution of the routine diagnostic methods used and/or as a consequence of the complex nomenclature associated with this group of organisms.

Purpura fulminans in a child secondary to Panton-Valentine leukocidin-producing Staphylococcus aureus.

A case of purpura fulminans (PF) in a child secondary to infection with meticillin-sensitive Staphylococcus aureus (MSSA) encoding the Panton-Valentine leukocidin (PVL) toxin genes is presented. Occasional cases of PF have been documented secondary to S. aureus infection in adults, but, to the authors' knowledge, not in children. Here the first UK case of MSSA-PVL leading to PF is presented.

Mixed Salmonella infection: case report and review of the literature.

Mixed infection with multiple Salmonella serotypes in the same patient is an unusual finding. We present a case of enteric fever in which both Salmonella Typhi and Salmonella Paratyphi A were isolated from the blood of a patient traveling from India.

Group A streptococcal meningitis: case report and review of the literature.

Group A streptococcus is an uncommon cause of meningitis in children. We report a single case of Group A streptococcus meningitis, in an apparently healthy 6-week-old infant. Twenty-five cases in the English-language literature in the last 25 years and our case are reviewed. The commonest associated illness was otitis media. Of the 25 patients, 24 survived. Antibiotic therapy, which consisted of penicillin in the majority of patients, was effective. Ceftriaxone was an alternative agent. Neurological sequelae were not uncommon. This report emphasizes the fact that Group A streptococcus can cause meningitis in healthy children without apparent recognizable foci of infection.