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BackgroundTick-borne encephalitis virus (TBEV) is a flavivirus spread by ticks and can cause tick-borne encephalitis (TBE) in humans. Previously, TBE has been reported in returning travellers in the United Kingdom (UK), but in 2019 and 2020, two probable cases of TBE acquired in the UK were identified.AimThe aim of this study was to investigate TBE cases in the UK between 2015 and 2023, describing the incidence, place and mode of acquisition and diagnostic process.MethodsA retrospective review of possible, probable and confirmed cases of TBE diagnosed by the Rare and Imported Pathogens Laboratory (RIPL) between January 2015 and December 2023 was performed. For cases identified in 2022 and 2023, clinical data were collected for enhanced surveillance using structured case record forms. Laboratory diagnosis is reviewed and described.ResultsWe identified 21 cases: three possible, seven probable and 11 confirmed cases. Of these, 12 were between January 2022 and December 2023: three possible, three probable and six confirmed cases. Two confirmed TBE cases had definite or highly probable acquisition in the UK, in June and August 2022, respectively. One of the possible cases had definite UK acquisition. Cases typically have a biphasic presentation, with encephalitis in the second phase.ConclusionClinicians should be aware of the possibility of TBE when the cause for encephalitis is not identified, even in the absence of travel to previously identified endemic regions.

Background: Characteristics of confirmed urogenital Schistosoma haematobium infections and outcomes in non-endemic regions are scarce in the literature and there is a minimal evidence base for appropriate management in this setting. Specific schistosomal urinary and urological complications include risk of hydronephrosis, renal impairment, and malignant transformation. Therefore, approach to follow-up should be robust and systematic., Methods: This is a retrospective case-note review of all patients with confirmed S haematobium infection (defined as visible ova in terminal urine and/or histopathological diagnosis on biopsy) at the Hospital for Tropical Diseases (HTD), London, between 1998 and 2018. Outcomes of follow-up were reviewed and formulated into a pragmatic guideline for follow-up of these patients in this setting., Results: A majority of the 186 patients with confirmed S haematobium infection presented before 2012. Young, male migrants were at highest risk of complications from chronic infection and were most prone to being lost to follow-up. One patient was referred with squamous cell carcinoma of the bladder found on biopsy with S haematobium infection., Conclusions: We put forward a pragmatic pathway for S haematobium investigation and follow-up for patients presenting to nonendemic settings with the current resource capabilities of the United Kingdom., Competing Interests: Potential conflicts of interest. There are no conflicts of interest among the authors of this paper., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: To report on the implementation and outcomes of a virtual ward established for the management of mpox during the 2022 outbreak, we conducted a 2-center, observational, cross-sectional study over a 3-month period., Methods: All patients aged ≥17 years with laboratory polymerase chain reaction-confirmed monkeypox virus managed between 14 May and 15 August 2022, at the Hospital for Tropical Diseases at University College London Hospitals National Health Service (NHS) Foundation Trust and sexual health services at Central North and West London NHS Foundation Trust, were included. Main outcomes included the proportion of patients managed exclusively on the virtual ward, proportion of patients requiring inpatient admission, proportion of patients with human immunodeficiency virus, and duration of lesion reepithelialization., Results: Among confirmed cases (N = 221), 86% (191/221) were managed exclusively on the virtual ward, while 14% (30/221) required admission. Treatment for concomitant sexually transmitted infections was provided to 25% (55/221) of patients, antibiotics for other infective complications to 16% (35/221), and symptomatic relief to 27% (60/221). The median time from onset to complete lesion reepithelialization and de-isolation was 18 days (range, 8-56 days). Eleven percent (24/221) of individuals disengaged from services within 4 days of testing., Conclusions: The virtual ward model facilitated safe and holistic outpatient management of mpox, while minimizing admissions. This approach could serve as a model for future outbreak responses., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

A 48-year-old man with poorly controlled HIV presented with severe human monkeypox virus (hMPXV) infection, having completed 2 weeks of tecovirimat at another hospital. He had painful, ulcerating skin lesions on most of his body and oropharyngeal cavity, with subsequent Ludwig's angina requiring repeated surgical interventions. Despite commencing a second, prolonged course of tecovirimat, he did not objectively improve, and new lesions were still noted at day 24. Discussion at the UK National Health Service England High Consequence Infectious Diseases Network recommended the use of 3% topical and then intravenous cidofovir, which was given at 5 mg/kg; the patient made a noticeable improvement after the first intravenous dose. He received further intravenous doses at 7 days and 21 days after the dose and was discharged at day 52. Cidofovir is not licensed for use in treatment of hMPXV infection. Data for cidofovir use in hMPXV are restricted to studies in animals. Four other documented cases of cidofovir use against hMPXV have been reported in the USA in 2022, but we present its first use in the UK. The scarcity of studies into the use of cidofovir in this condition clearly shows the need for robust studies to assess efficacy, optimum dosage, timing, and route of administration., Competing Interests: Declaration of interests DA-J has received consultancy fees or honoraria from Gilead and Pulmocide and has stock or stock options in Pulmocide. MG has received consultancy fees from Pfizer. FD receives a Clinical Academic Research Partnerships Fellowship from the Medical Research Council. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: The burden of imported rickettsial infection in the UK is not previously described. This retrospective review identifies rickettsial cases diagnosed at the national reference laboratory between 2015 and 2022., Methods: Samples testing positive for spotted fever group, typhus group, and scrub typhus IgG/IgM on acute and convalescent blood samples, and/or PCR on tissue/blood were categorized as suspected, confirmed or past infection., Results: 220 patients had rickettsioses, and the commonest import was acute spotted fever group infection (61%, 125/205), 54% (62/114) from South Africa. In acute typhus group cases, 60% (40/67) were from Southeast Asia. One patient with Rickettsia typhi bacteremia died. Scrub typhus group infections (5%, 10/205) were exclusively from Asia and the Western Pacific regions. Overall, 43% of confirmed cases (39/91) had not received doxycycline prior to results., Conclusions: Rickettsial infections are important and under-recognized causes of imported fever in the UK. Thorough history, examination, and timely treatment with doxycycline should be considered if there is suspicion of Rickettsia infection before testing., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A previously well man in his 50s returned to the UK after a trip to the Mediterranean. The day after returning he developed malaise, fevers, rigors and severe headache. He was hospitalised with sepsis, multiorgan involvement, a maculopapular rash and an eschar on each hip. Serology was positive for Rickettsia spp (spotted fever group) with a rise in titre from 1:64 to 1:1024 eight days later. Blood and tissue PCR were also positive for Rickettsia spp. He had cardiac, pulmonary, renal, ocular and neurological involvement. He completed a 14-day course of doxycycline and recovered well. This is a case of likely Mediterranean spotted fever (MSF) caused by Rickettsia conorii, which is endemic to the Mediterranean basin. We highlight the need for awareness and early treatment to prevent severe complications. This case is also the first to describe Purtscher-like retinopathy in the context of likely MSF., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Lower respiratory infections constitute a major disease burden worldwide. Treatment is usually empiric and targeted towards typical bacterial pathogens. Understanding the prevalence of pathogens not covered by empirical treatment is important to improve diagnostic and treatment algorithms., Methods: A prospective observational study in peri-urban communities of Yangon, Myanmar was conducted between July 2018 and April 2019. Sputum specimens of 299 adults presenting with fever and productive cough were tested for Mycobacterium tuberculosis (microscopy and GeneXpert MTB/RIF [Mycobacterium tuberculosis/resistance to rifampicin]) and Burkholderia pseudomallei (Active Melioidosis Detect Lateral Flow Assay and culture). Nasopharyngeal swabs underwent respiratory virus (influenza A, B, respiratory syncytial virus) polymerase chain reaction testing., Results: Among 299 patients, 32% (95% confidence interval [CI] 26 to 37) were diagnosed with tuberculosis (TB), including 9 rifampicin-resistant cases. TB patients presented with a longer duration of fever (median 14 d) and productive cough (median 30 d) than non-TB patients (median fever duration 6 d, cough 7 d). One case of melioidosis pneumonia was detected by rapid test and confirmed by culture. Respiratory viruses were detected in 16% (95% CI 12 to 21) of patients., Conclusions: TB was very common in this population, suggesting that microscopy and GeneXpert MTB/RIF on all sputum samples should be routinely included in diagnostic algorithms for fever and cough. Melioidosis was uncommon in this population., (© The Author(s) 2021. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: Cryptococcal meningitis (CM) is a common HIV-associated opportunistic-infection worldwide. Existing literature focusses on hospital-based outcomes of induction treatment. This paper reviews outpatient management in integrated primary care clinics in Yangon., Method: This retrospective case note review analyses a Myanmar HIV-positive patient cohort managed using ambulatory induction-phase treatment with intravenous amphotericin-B-deoxycholate (0.7-1.0 mg/kg) and oral fluconazole (800 mg orally/day)., Results: Seventy-six patients were diagnosed between 2010 and 2017. The median age of patients diagnosed was 35 years, 63% were male and 33 (45%) were on concurrent treatment for tuberculosis. The median CD4 count was 60 at the time of diagnosis. Amphotericin-B-deoxycholate infusions precipitated 56 episodes of toxicity, namely hypokalaemia, nephrotoxicity, anaemia, febrile reactions, phlebitis, observed in 44 patients (58%). One-year survival (86%) was higher than existing hospital-based treatment studies., Conclusion: Ambulation of patients in this cohort saved 1029 hospital bed days and had better survival outcomes when compared to hospital-based studies in other resource constrained settings.

Background: While a number of predictors for Ebola mortality have been identified, less is known about post-viral symptoms. The identification of acute-illness predictors for post-viral symptoms could allow the selection of patients for more active follow up in the future, and those in whom early interventions may be beneficial in the long term. Studying predictors of both mortality and post-viral symptoms within a single cohort of patients could also further our understanding of the pathophysiology of survivor sequelae., Methods/principal Findings: We performed a historical cohort study using data collected as part of routine clinical care from an Ebola Treatment Centre (ETC) in Kerry Town, Sierra Leone, in order to identify predictors of mortality and of post-viral symptoms. Variables included as potential predictors were sex, age, date of admission, first recorded viral load at the ETC and symptoms (recorded upon presentation at the ETC). Multivariable logistic regression was used to identify predictors. Of 263 Ebola-confirmed patients admitted between November 2014 and March 2015, 151 (57%) survived to ETC discharge. Viral load was the strongest predictor of mortality (adjusted OR comparing high with low viral load: 84.97, 95% CI 30.87-345.94). We did not find evidence that a high viral load predicted post-viral symptoms (ocular: 1.17, 95% CI 0.35-3.97; musculoskeletal: 1.07, 95% CI 0.28-4.08). Ocular post-viral symptoms were more common in females (2.31, 95% CI 0.98-5.43) and in those who had experienced hiccups during the acute phase (4.73, 95% CI 0.90-24.73)., Conclusions/significance: These findings may add epidemiological support to the hypothesis that post-viral symptoms have an immune-mediated aspect and may not only be a consequence of high viral load and disease severity., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Determining the cause of eosinophilia in patients returning from the tropics continues to present a diagnostic challenge. The history, symptoms and degree of eosinophilia are often poor predictors of eventual diagnosis, but helminths are an important cause. The current British Infection Association recommendations use travel history to guide investigation of eosinophilia. However the global burden of helminth disease and travel patterns have changed over the last 3 decades and guidelines based on previous epidemiology need to be reviewed in the light of current data., Methods: Consecutive patients presenting with, or referred for, investigation of eosinophilia were identified prospectively. Case notes, laboratory results and electronic records were reviewed for demographic and clinical data. Patients with an eosinophil count ≥0.50 × 10 9 /L were included, and grouped based on lifetime history of travel to: West Africa, elsewhere in Africa, and the rest of the world. Results were compared to published data from 1997 to 2002 collected at the same centre., Results: Of 410 patients who met the inclusion criteria, 407 had a documented travel history. Average yearly referrals for eosinophilia fell from 58 per year between 1997 and 2002, to 33 per year (2002-2015). The proportion of eosinophilia cases diagnosed with a parasitic cause fell from 64% to 50%, and yields for all parasitological investigations fell, the largest reduction in stool microscopy (20% yield to 9%) and day bloods for microfilariae (14% yield to 3%). Strongyloides stercoralis was the commonest diagnosis overall in our cohort, accounting for 50% of the total parasites diagnosed, and was present in 38% of patients from West Africa, 19% from rest of Africa, and 34% from rest of world; a relative increase compared to previous data. Schistosomiasis is slightly less common in those who had travelled to West Africa than the rest of Africa, and overall point prevalence has fallen from 33% (1997-2002) to 17% (2002-2015). Travellers were significantly less likely than patients who had immigrated to the UK to be diagnosed with any parasite (OR 0.54 95% CI 0.378-0.778 p = 0.0009)., Discussion: A parasitic cause will still be found in half of people returning from the tropics with an eosinophilia, but we observed a fall in the overall prevalence of parasitic diagnoses when compared with the earlier data. This may, in part, be explained by the impact of control programmes on the prevalence of parasites globally, especially filarial disease. S. stercoralis now represents the majority of parasites diagnosed in our cohort from all continents. We identified significantly higher rates of strongyloidiasis in immigrants than returning travellers. Despite the falling yields of stool microscopy and filarial serology the current guidelines based on travel history remain relevant with adequate yield., (Copyright © 2017 The British Infection Association. All rights reserved.)

Primary cerebral phaeohyphomycosis due to Rhinocladiella mackenziei is an extremely rare infection carrying more than 80% mortality, with most cases reported from the Middle East region. This darkly pigmented black yeast is highly neurotropic, aggressive and refractory to most antifungal agents. Here we present an immunocompetent elderly male, presenting with multiple brain abscesses, with R. mackenziei confirmed by nuclear ribosomal repeat region sequencing, who was successfully treated by surgical debridement and intravenous voriconazole. To our knowledge this is the first case reported from the United Kingdom. We also present a review of all such cases so far reported in the English literature world-wide, which we believe is a step further to understanding the pathogenesis and establishing effective treatment of this rare, yet often fatal disease.

Activation of the PI3K/Akt pathway protects the heart from ischemia-reperfusion injury (IRI). The phosphatase PTEN is the main negative regulator of this pathway. We hypothesized that reduced PTEN levels could protect against IRI. Isolated perfused mouse hearts from PTEN(+/-) and their littermates PTEN(+/+) (WT), were subjected to 35 min global ischemia and 30 min reperfusion, with and without 2, 4 or 6 cycles ischemic preconditioning (IPC). The end point was infarct size, expressed as a percentage of the myocardium at risk (I/R%). PTEN and Akt levels were determined using Western blot analysis. Unexpectedly, there were no significant differences in infarction between PTEN(+/-) and WT (42.1 +/- 5.0% Vs. 45.6 +/- 3.3%). However, the preconditioning threshold was significantly reduced in the PTEN(+/-) Vs. WT, with 4 cycles of IPC being sufficient to reduce I/R%, compared to 6 cycles in the WT (4 cycles IPC: 29.8. +/- 3.69% in PTEN(+/-) Vs. 45.5. +/- 5.08% in WT, P < 0.01). In addition, the ratio between the phospho/total Akt (Ser473 and Thr308) was slightly but significantly increased in the PTEN(+/-) indicating an upregulation of PI3K/Akt pathway. Interestingly, the levels of the other phosphatases that may negatively regulate the PI3K/Akt pathway (PP2A, SHIP2 and PHLPP) were not significantly different between littermates and PTEN(+/-). In conclusion, PTEN haploinsufficiency alone does not induce cardioprotection in this model; however, it reduces the threshold of protection induced by IPC.