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High-content imaging (HCI) provides quantitative and information-rich measurements of chemical effects on human in vitro cell models. Identification of discriminative phenotypic endpoints from cellular features obtained from HCI is required for accurate assessments of potential chemical hazards. However, the use of suboptimal metrics to quantify the concentration-response curves (CRC) of chemicals based on these features may obscure discriminative features, and lead to non-predictive endpoints and poor chemical classifications or hazard assessments. Here, we present a systematic and data-driven study on the performances of different CRC metrics in identifying image-based phenotypic features that can accurately classify the effects of reference chemicals with known in vivo toxicities. We studied four previous HCI in vitro nephro- or pulmono-toxicity datasets, which contain phenotypic feature measurements from different cell and feature types. Within a feature type, we found that efficacy metrics at higher chemical concentrations tend to give higher classification accuracy, whereas potency metrics do not have obvious trends across different response levels. Across different cell and feature types, efficacy metrics generally gave higher classification accuracy than potency metrics and area under the curve (AUC). Our results suggest that efficacy metrics, especially at higher concentrations, are more likely to help us to identify discriminative phenotypic endpoints. Therefore, HCI experiments for toxicological applications should include measurements at sufficiently high chemical concentrations, and efficacy metrics should always be analyzed. The identified features may be used as specific toxicity endpoints for further chemical hazard assessment.

Some people with COVID‐19 will need support for physical, emotional and mental symptoms long after they have recovered from the acute phase of the infection. Many of those with so‐called ‘long Covid’ are likely to have a post‐viral condition very similar to chronic fatigue syndrome/myalgic encephalomyelitis for which management guidelines and a network of NHS clinics already exist.

A new 3-year curriculum for training in internal medicine was approved by the General Medical Council in December 2017. This will replace core medical training in August 2019. It mandates specific experiences and introduces a novel assessment strategy that hopefully will lessen the perceived ‘burden of assessment’ on trainees (and trainers). It is hoped that it will improve the experience of and enthusiasm for training in internal medicine.

OBJECTIVES To define the status of Infectious Diseases (ID) as an approved specialty in Europe; to enumerate the number of specialists (in general and in relation to the overall population) and specialist trainees and describe the content, delivery, and evaluation of postgraduate training in ID in different countries. METHODS Structured web-based questionnaire surveys in March 2021 of responsible national authorities, specialist societies and individual country representatives to the Section of Infectious Diseases of the European Union for Medical Specialties. Descriptive analysis of quantitative and qualitative responses. RESULTS In responses received from 33/35 (94.3%) countries, ID is recognised as a specialty in 24 and as a subspecialty of general internal medicine (GIM) in 8, but it is not recognised in Spain. The number of ID specialists per country varies from

Human lungs are susceptible to the toxicity induced by soluble xenobiotics. However, the direct cellular effects of many pulmonotoxic chemicals are not always clear, and thus, a general in vitro assay for testing pulmonotoxicity applicable to a wide variety of chemicals is not currently available. Here, we report a study that uses high-throughput imaging and artificial intelligence to build an in vitro pulmonotoxicity assay by automatically comparing and selecting human lung-cell lines and their associated quantitative phenotypic features most predictive of in vivo pulmonotoxicity. This approach is called “High-throughput In vitro Phenotypic Profiling for Toxicity Prediction” (HIPPTox). We found that the resulting assay based on two phenotypic features of a human bronchial epithelial cell line, BEAS-2B, can accurately classify 33 reference chemicals with human pulmonotoxicity information (88.8% balance accuracy, 84.6% sensitivity, and 93.0% specificity). In comparison, the predictivity of a standard cell-viability assay on the same set of chemicals is much lower (77.1% balanced accuracy, 84.6% sensitivity, and 69.5% specificity). We also used the assay to evaluate 17 additional test chemicals with unknown/unclear human pulmonotoxicity, and experimentally confirmed that many of the pulmonotoxic reference and predicted-positive test chemicals induce DNA strand breaks and/or activation of the DNA-damage response (DDR) pathway. Therefore, HIPPTox helps us to uncover these common modes-of-action of pulmonotoxic chemicals. HIPPTox may also be applied to other cell types or models, and accelerate the development of predictive in vitro assays for other cell-type- or organ-specific toxicities. Electronic supplementary material The online version of this article (10.1007/s00204-018-2213-0) contains supplementary material, which is available to authorized users.

© 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Viral meningitis is increasingly recognised, but little is known about the frequency with which it occurs, or the causes and outcomes in the UK. We aimed to determine the incidence, causes, and sequelae in UK adults to improve the management of patients and assist in health service planning. Methods: We did a multicentre prospective observational cohort study of adults with suspected meningitis at 42 hospitals across England. Nested within this study, in the National Health Service (NHS) northwest region (now part of NHS England North), was an epidemiological study. Patients were eligible if they were aged 16 years or older, had clinically suspected meningitis, and either underwent a lumbar puncture or, if lumbar puncture was contraindicated, had clinically suspected meningitis and an appropriate pathogen identified either in blood culture or on blood PCR. Individuals with ventricular devices were excluded. We calculated the incidence of viral meningitis using data from patients from the northwest region only and used these data to estimate the population-standardised number of cases in the UK. Patients self-reported quality-of-life and neuropsychological outcomes, using the EuroQol EQ-5D-3L, the 36-Item Short Form Health Survey (SF-36), and the Aldenkamp and Baker neuropsychological assessment schedule, for 1 year after admission. Findings: 1126 patients were enrolled between Sept 30, 2011, and Sept 30, 2014. 638 (57%) patients had meningitis: 231 (36%) cases were viral, 99 (16%) were bacterial, and 267 (42%) had an unknown cause. 41 (6%) cases had other causes. The estimated annual incidence of viral meningitis was 2·73 per 100 000 and that of bacterial meningitis was 1·24 per 100 000. The median length of hospital stay for patients with viral meningitis was 4 days (IQR 3–7), increasing to 9 days (6–12) in those treated with antivirals. Earlier lumbar puncture resulted in more patients having a specific cause identified than did those who had a delayed lumbar puncture. Compared with the age-matched UK population, patients with viral meningitis had a mean loss of 0·2 quality-adjusted life-years (SD 0·04) in that first year. Interpretation: Viruses are the most commonly identified cause of meningitis in UK adults, and lead to substantial long-term morbidity. Delays in getting a lumbar puncture and unnecessary treatment with antivirals were associated with longer hospital stays. Rapid diagnostics and rationalising treatments might reduce the burden of meningitis on health services. Funding: Meningitis Research Foundation and UK National Institute for Health Research.

Background: Concerns about over-diagnosis and inappropriate management of Lyme disease (LD) are well documented in North America and supported by clinical data. There are few parallel data on the situation in the UK. Aim: To describe the patterns of referral, investigation, diagnosis and treatment of patients with suspected LD referred to an infectious disease unit in Liverpool, UK. Previous management by National Health Service (NHS) and non-NHS practitioners was reviewed. Design: Descriptive study conducted by retrospective casenotes review. Methods: Retrospective casenotes review of adults referred with possible LD to an infectious disease unit in Liverpool, UK, over 5 years (2006–2010). Results: Of 115 patients, 27 (23%) were diagnosed with LD, 38 (33%) with chronic fatigue syndrome (CFS) and 13 (11%) with other medical conditions. No specific diagnosis could be made in 38 (33%). At least 53 unnecessary antibiotic courses had been given by non-NHS practitioners; 21 unnecessary courses had been prescribed by NHS practitioners. Among 38 patients, 17 (45%) with CFS had been misdiagnosed as having LD by non-NHS practitioners. Conclusions: A minority of referred patients had LD, while a third had CFS. LD is over-diagnosed by non-specialists, reflecting the complexities of clinical and/or laboratory diagnosis. Patients with CFS were susceptible to misdiagnosis in non-NHS settings, reinforcing concerns about missed opportunities for appropriate treatment for this group and about the use of inappropriate diagnostic modalities and anti-microbials in non-NHS settings.

Background Survivors of bacterial meningitis are known to suffer neuropsychological deficits after their acute illness. Previous studies have suggested that viral meningitis may also cause cognitive problems. Primary and Objective We aimed to determine what the neuropsychological problems encountered by adults with viral meningitis were compared to healthy patients without meningitis and how long their problems lasted. Methods Patients with viral meningitis and healthy controls completed the ‘Aldenkamp and Baker Neuropsychological Assessment Schedule (ABNAS)’, a 24 item self-administered questionnaire. Patients completed the ABNAS at 4 time points – 6, 12, 24 and 48 weeks post acute illness. Higher ABNAS scores correspond to greater levels of neuropsychological dysfunction, with a worst score possible of 72. Results Healthy controls (n=224) had a mean total ABNAS score of 7. Comparatively, the patients with viral meningitis had significantly worse scores at all 4 time points. At 6 weeks scoring 22 (p Conclusions Patients with viral meningitis have significantly worse neuropsychological deficits compared to healthy controls. The deficits showed some improvement initially but failed to improve significantly beyond 24 weeks.

Background As bacterial meningitis decreases in incidence, viral meningitis becomes relatively more important. The incidence and costs of viral meningitis in adults are unknown. Methods An epidemiological study of adults with suspected meningitis in England, was carried out between 2011 and 2014. We estimated incidence and healthcare costs using patient level data from the Northwest of England, and extrapolated to estimate resource use throughout the UK. Results Among 1117 patients enrolled, 638 (57%) had meningitis. 231/638 (36%) had viral meningitis, 99/638 (16%) bacterial and 267/638 (42%) unknown aetiology. Estimated annual incidences of viral and bacterial meningitis were 2.73 and 1.24 per 1 00 000 respectively. The yearly healthcare cost of viral and bacterial meningitis were similar: £3,220,343 (95% CI £1,206,963 – £4,418,424) and £4,860,218 (95% CI £3,728,598 – £6,358,419) respectively, p=0.57. The median length of stay for patients with viral meningitis was 4 days, increasing to 8 days in those treated with antivirals, which are of no proven benefit. Hospitalisation accounted for 79% of the cost. Conclusions Viral meningitis is the predominant cause of meningitis in adults in the UK. The total annual healthcare costs could be reduced by earlier discharge. This might be achieved through speedier diagnostics and avoiding unnecessary treatments.

Objectives Appropriate assessment of community-acquired pneumonia (CAP) allows accurate severity scoring and hence optimal management, leading to reduced morbidity and mortality. British Thoracic Society (BTS) guidelines provide an appropriate score. Adherence to BTS guidelines was assessed in our medical assessment unit (MAU) in 2001/2 and again in 2005/6, 3 years after introducing an educational programme. Methods A retrospective case-note study, comparing diagnosis, documentation of severity, management and outcome of CAP during admission to MAU during 3 months of each winter in 2001/2 and 2005/6. Results In 2001/2, 65/165 patients were wrongly coded as CAP and 100 were included in the study. In 2005/6 43/130 were excluded and 87 enrolled. In 2005/6, 87% did not receive a severity score, a significant increase from 48% in 2001/2 (p Conclusions Coding remains poor. Adherence to CAP management guidelines was poor and has significantly worsened. Educational programmes, alone, do not improve adherence. Restriction of antibiotic prescribing should be considered.

Introduction\ud \ud Chronic hepatitis B virus and schistosomiasis are independently associated with significant mortality and morbidity worldwide. Despite much geographic overlap between these conditions and no reason why co-infection should not exist, we present what is, to the best of our knowledge, the first published report of a proven histological diagnosis of hepatic Schistosomiasis japonicum and chronic hepatitis B co-infection. A single case of hepatitis B and hepatic Schistosomiasis mansoni diagnosed by liver biopsy has previously been reported in the literature.\ud \ud Case presentation\ud \ud A 38-year-old Chinese man with known chronic hepatitis B virus infection presented with malaise, nausea and headache. Blood tests revealed increased transaminases and serology in keeping with hepatitis B virus e-antigen seroconversion. A liver biopsy was performed because some investigations, particularly transient elastography, suggested cirrhosis. Two schistosome ova were seen on liver histology, identified as S. japonicum, probably acquired in China as a youth. His peripheral eosinophil count was normal, schistosomal serology and stool microscopy for ova, cysts and parasites were negative.\ud \ud Conclusion\ud \ud Hepatic schistosomiasis co-infection should be considered in patients with hepatitis B virus infection who are from countries endemic for schistosomiasis. Screening for schistosomiasis using a peripheral eosinophil count, schistosomal serology and stool microscopy may be negative despite infection, therefore presumptive treatment could be considered. Transient elastography should not be used to assess liver fibrosis during acute flares of viral hepatitis because readings are falsely elevated. The impact of hepatic schistosomiasis on the sensitivity and specificity of transient elastography measurement for the assessment of hepatitis B is as yet unknown.

Chylothorax is a rare complication of visceral Kaposi’s sarcoma. We report a case with bilateral chylothoraces secondary to relapsed visceral Kaposi’s sarcoma who was successfully treated with paclitaxel chemotherapy.

During the 1980s and early 1990s, the advocacy group ACT UP (AIDS Coalition To Unleash Power) had a slogan: ‘ignorance = fear, silence = death’.1 McElveen’s comment on information silence about HIV infection between primary and secondary care reminds us that the message is still relevant today. However, the solution is more complicated than making communication of a patient’s HIV status to their GP automatic. HIV infection hidden from primary health care is already a sizeable challenge: 20–49% of people living with HIV choose not to disclose their status to GPs;2–8 a legacy …

Copyright: © 2013 Miller A. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. At first sight this seems a question with an obvious response and not one that requires debate in the editorial columns of a tropical medicine journal. However, the answer may be more complex than appears at first sight and perhaps it may therefore benefit from a more detailed exploration. The obvious response is that the discipline of “Tropical Medicine” refers to the practice of medicine in the tropics. But does it refer to all medical practice that takes place within the Tropics, does it refer to the practice of medicine within resource poor settings or does it refer to the diagnosis and treatment of infectious and parasitic diseases found in a tropical environment? There is no standard definition of Tropical Medicine. In the UK, doctors who wish to specialize in Tropical Medicine (TM) must first train in General Internal Medicine (GIM) and secure their exam to gain Membership of the Royal College of Physicians (MRCP). They then follow the training pathway for specialists in Infectious Disease (ID) with the addition of doing a full time course of study for the Diploma of Tropical Medicine & Hygiene (DTM&H). Study is carried out at either the London or Liverpool Schools of Tropical Medicine and the diploma is conferred either by the Royal College of Physicians of London or the Liverpool School of Tropical Medicine. Additionally trainees who wish to be certified in TM must spend at least 2 years of their training at the UK centre approved for TM training (currently Liverpool, London and Birmingham) and spend a year working overseas in a resource poor setting. In many other countries, TM does not exist as a distinct specialty but is incorporated into the practice of Infectious Disease. In the US, it is not a board certified specialty but there are several credentialed courses available. These days, Tropical Medicine is often referred to as global/geographical health or international health and it encompasses a number of sub specialties such as refugee healthcare, travel medicine and expedition or remote/wilderness medicine.

Background. Our aim was to document how often travel histories were taken and the quality of their content. Methods. Patients admitted over 2 months to acute medical units of two hospitals in the Northwest of England with a history of fever, rash, diarrhea, vomiting, jaundice, or presenting as “unwell post-travel” were identified. The initial medical clerking was assessed. Results. A total of 132 relevant admissions were identified. A travel history was documented in only 26 patients (19.7%). Of the 16 patients who had traveled, there was no documentation of pretravel advice or of sexual/other activities abroad in 15 (93.8%) and 12 (75.0%) patients, respectively. Conclusions. There needs to be better awareness and education about travel-related illness and the importance of taking an adequate travel history.

Introduction: Bacterial meningitis is a medical emergency, the outcome of which is improved by prompt antibiotic treatment. For patients with suspected meningitis and no features of severe disease, the British Infection Society recommends immediate lumbar puncture (LP) before antibiotics, to maximise the chance of a positive cerebrospinal (CSF) culture. In such patients, CT scanning before LP is not needed.\ud \ud Methods: The case notes of adults with meningitis admitted to a large district general hospital over 3 years were reviewed. Patients were classified as Likely Bacterial Meningitis or Likely Viral Meningitis based on their CSF and peripheral blood results using the Meningitest Criteria, with microbiological and virological confirmation.\ud \ud Results: Of 92 patients studied, 24 had Likely Bacterial Meningitis, including 16 with microbiologically confirmed disease (none had PCR tests for bacteria). Sixty-eight had Likely Viral Meningitis, four of whom had viral PCR, including one with herpes simplex virus. No patient had an LP before antibiotics. CSF culture was positive for eight (73%) of the 11 patients who had an LP up to 4 h after starting antibiotics, compared with eight (11%) of 71 patients with a later LP (p

Introduction Acute Human Immunodeficiency Virus infection is associated with a range of neurological conditions. Guillain-Barré syndrome is a rare presentation; acute inflammatory demyelinating polyneuropathy is the commonest form of Guillain-Barré syndrome. Acute inflammatory demyelinating polyneuropathy has occasionally been reported in acute Immunodeficiency Virus infection but little data exists on frequency, management and outcome. Case presentation We describe an episode of Guillain-Barré syndrome presenting as acute inflammatory demyelinating polyneuropathy in a 30-year-old man testing positive for Immunodeficiency Virus, probably during acute seroconversion. Clinical suspicion was confirmed by cerebrospinal fluid analysis and nerve conduction studies. Rapid clinical deterioration prompted intravenous immunoglobulin therapy and early commencement of highly active anti-retroviral therapy. All symptoms resolved within nine weeks. Conclusion Unusual neurological presentations in previously fit patients are an appropriate indication for Immunodeficiency-Virus testing. Highly active anti-retroviral therapy with adequate penetration of the central nervous system should be considered as an early intervention, alongside conventional therapies such as intravenous immunoglobulin.

Purpose Cytomegalovirus (CMV) retinitis classically occurs in advanced human immunodeficiency virus (HIV) infection but is rare in other forms of immunosuppression. The authors report a case of CMV retinitis in an HIV-negative man with idiopathic CD4 lymphocytopenia (ICL). This is the first such case to be confirmed by polymerase chain reaction (PCR) of aqueous humor. Methods Case report. Results A 69-year-old retired Chinese seaman presented with gradual visual deterioration. He was a diet controlled diabetic on regular steroids for presumed asthma. Examination showed no diabetic eye disease but confirmed acute retinal necrosis (ARN). Anterior chamber tapping of the aqueous humor was PCR positive for CMV. HIV antibody and RNA tests were negative but his full blood count revealed lymphocytopenia, with a low CD4+ subset. He responded to a 3-week course of intravenous ganciclovir therapy followed by suppressive oral valganciclovir. Conclusions CMV is associated with sight-threatening retinitis in HIV infection at CD4+ counts below 50 cells/μL and in transplant recipients or heavily immunosuppressed patients. Systemic steroids are a risk factor for clinical disease in these groups. It is extremely rare to report CMV eye disease in previously healthy individuals. This case illustrates that the condition does occur in association with ICL. Corticosteroids may be implicated in disease reactivation. Molecular methods are necessary to confirm the diagnosis.

Background: Nucleic acid amplification tests (NAAT) based on PCR provide rapid identification of Mycobacterium tuberculosis and the detection of rifampicin resistance. Indications for their use in clinical samples are now included in British tuberculosis guidelines. Methods: A retrospective audit of patients with suspected mycobacterial infection in a Liverpool hospital between 2002 and 2006. Documentation of the impact of NAAT usage in acid fast bacillus (AFB) microscopy positive samples on clinical practice and the influence of a multidisciplinary group on their appropriate use, compared with British guidelines. Results: Mycobacteria were seen or isolated from 282 patients and identified as M tuberculosis in 181 (64%). NAAT were indicated in 87/123 AFB positive samples and performed in 51 (59%). M tuberculosis was confirmed or excluded by this method in 86% of tested samples within 2 weeks, compared with 7% identified using standard methods. The appropriate use of NAAT increased significantly over the study period. The NAAT result had a clinical impact in 20/51 (39%) tested patients. Culture results suggest the potential for a direct clinical impact in 8/36 (22%) patients in which it was indicated but not sent and 5/36 (14%) patients for whom it was not indicated. Patients managed by the multidisciplinary group had a higher rate of HIV testing and appropriate use of NAAT. Conclusions: There were significant clinical benefits from the use of nucleic acid amplification tests in this low prevalence setting. Our data suggest that there would be additional benefit from their use with all AFB smear positive clinical samples.

Since the terrorist attack on the United States in September 2001 attention has been focused on the threat of biological warfare. The disruptive effects of deliberate release of anthrax in civilian settings have been well documented, and several other pathogens could also be used as biological weapons. We have described the key features of such pathogens, how they might be used in biological warfare, and the clinical syndromes they cause. We also discuss the medical and logistic response to their possible use. #### Summary points Appropriate dispersion of even a small volume of biological warfare agent may cause high morbidity and mortality, which may be exacerbated by public panic and social disruption Early symptoms of disease induced by a biological warfare agent may be non-specific or difficult to recognise Healthcare workers should be alert for unusual single cases or clusters of illness, especially in otherwise healthy adults Unusual illness should be notified immediately to public health authorities Strategic responses to the deliberate release of biological warfare agents must be rehearsed locally and nationally with multiple agencies Healthcare professionals should familiarise themselves with national and local sources of advice on deliberate release Biological warfare agents are defined as “living organisms, whatever their nature, or infected material derived from them, which are used for hostile purposes and intended to cause disease or death in man, animals and plants, and which depend for their efforts on the ability to multiply in the person, animal or plant attacked.”1 Many such agents are zoonotic and have a considerable impact on agriculture as well as on human health. Biological warfare agents are well suited for use in bioterrorism or for attack by poorer nations against the rich (so called “asymmetric methods” of attack2) as they are cheap and easy to obtain and disperse, although full scale use …

British and Australian medical teams working in Northern Iraq in 1991 providing primary care to refugees and the war wounded were subjected to a descriptive retrospective survey, 5 weeks after arriving in Iraq. The aim was to document different rates of diarrhea in British and Australian troops. The British, who were not taking daily doxycycline and did not enforce a plate- and hand-washing routine, experienced higher rates of diarrhea (69% of British troops compared with 36% of Australian troops), which was more severe and of a longer duration (p < 0.001) and resulted in twice as many days being lost (p < 0.001) in spite of the British team being half the size of the Australian contingent, and the region having enteropathogens with a high rate of antibiotic resistance. Vigorous hand- and plate-washing routines along with doxycycline prophylaxis appear to significantly reduce incapacitation from diarrhea in this military setting and have an important implication for operational effectiveness.

Godlee suggests that adoption of the Canadian criteria to diagnose chronic fatigue syndrome (CFS) is a reasonable request.1 It may be reasonable but is probably not practicable. These criteria require the assessment of some 65 discrete symptoms and 14 comorbid conditions before even considering exclusionary …

A 23-year-old soldier developed a facial ulcer after returning from Belize. The possibility of cutaneous leishmaniasis prompted referral to our unit. The lesion was photographed with a mobile phone and texted to a secure webpage with password access (fi gure). The images supported the diagnosis of cutaneous leishmaniasis and the patient was admitted. The diagnosis was confi rmed histologically and the parasites found to be Leishmania braziliensis. The patient was treated as an inpatient with a standard regimen of 20 mg/kg of intravenous sodium stibogluconate for 20 days. This therapy led to an uneventful recovery, with no relapse at 6 months follow-up. Although image transfer in medicine is not new, using mobile phone digital imaging is. Its role is likely to expand and aid rapid diagnosis from remote areas. Lancet Infect Dis 2006; 6: 455