Musculoskeletal manifestations of Ebola virus.

The 2014 West African Ebola virus disease outbreak shocked the world as it swept through the region leaving Guinea, Liberia and Sierra Leone struggling to gain control. As the largest Ebola virus disease outbreak to date, there are more survivors in its wake than ever before, with a spectrum of health problems requiring management. Here we review various musculoskeletal manifestations of the virus that can occur both during and after the infection, and consider possible pathogenesis.

Ebola virus as a sexually transmitted infection.

PURPOSE OF REVIEW: The ongoing Ebola virus epidemic in West Africa is a major global health challenge. The main mode of transmission is through contact with bodily fluids and skin of those infected or who have died. This review was undertaken to consider the evidence for transmission by contact with bodily fluids occurring through sexual activity. RECENT FINDINGS: No cases in the previous 20 outbreaks or the current outbreak in West Africa have been shown to be sexually transmitted, although other types of viral haemorrhagic fever have had sexual transmission implicated. Ebola virus is found in sites and fluids associated with sexual activity but this occurs at different stages of the disease. Persistence in the convalescent period occurs in rectum, vagina and semen, with persistence in semen being longest of up to at least 101 days. Recommendations based on this data are that those recovering from Ebola virus disease should abstain from all sexual intercourse, or if this is not possible, use condoms, for 3 months after the onset of symptoms. SUMMARY: There is theoretical plausibility for sexual transmission of Ebola virus but there has been no evidence of this occurring. Further research is needed to consider if sexual activity contributes to the epidemic in order to inform individuals with regard to avoiding acquisition or transmission by those recovering from Ebola virus disease.

Clinical Management of Hospitalized Patients With High-Consequence Infectious Diseases in England.

Infectious disease physicians in England have been diagnosing and managing occasional cases of viral hemorrhagic fever since 1971, including the United Kingdom's first case of Ebola virus disease in 1976. Specialist isolation facilities to provide safe and effective care have been present since that time. Following the emergence of Middle East respiratory syndrome (MERS) in 2012, and the avian influenza A (H7N9) outbreak in 2013, and the 2014-2016 Ebola virus disease outbreak in West Africa, clinical and public health preparedness and response pathways in England have been strengthened for these types of diseases, now called high-consequence infectious diseases (HCIDs). The HCID program, led by NHS England and Public Health England between 2016 and 2018, helped to deliver these enhancements, which have since been used on multiple occasions for new UK cases and outbreaks of MERS, mpox, avian influenza, and Lassa fever. Additionally, HCID pathways were activated for COVID-19 during the first 3 months of 2020, before the pandemic had been declared and little was known about COVID-19 but HCID status had been assigned temporarily to COVID-19 as a precaution. The HCID program also led to the commissioning of a network of new airborne HCID treatment centers in England, to supplement the existing network of contact HCID treatment centers, which includes the United Kingdom's only 2 high-level isolation units. In this case study, the authors describe the airborne and contact HCID treatment center networks in England, including their formation and structures, their approach to safe and effective clinical management of patients with HCIDs in the United Kingdom, and challenges they may face going forward.

Monkeypox encephalitis with transverse myelitis in a female patient.

The 2022 monkeypox outbreak has affected 110 countries worldwide, outside of classic endemic areas (ie, west Africa and central Africa). On July 23, 2022, the outbreak was classified by WHO as a public health emergency of international concern. Clinical presentation varies from mild to life-changing symptoms; neurological complications are relatively uncommon and there are few therapeutic interventions for monkeypox disease. In this Grand Round, we present a case of monkeypox with encephalitis complicated by transverse myelitis in a previously healthy woman aged 35 years who made an almost complete recovery from her neurological symptoms after treatment with tecovirimat, cidofovir, steroids, and plasma exchange. We describe neurological complications associated with orthopoxvirus infections and laboratory diagnosis, the radiological features in this case, and discuss treatment options.

Clinical features and management of human monkeypox: a retrospective observational study in the UK.

BACKGROUND: Cases of human monkeypox are rarely seen outside of west and central Africa. There are few data regarding viral kinetics or the duration of viral shedding and no licensed treatments. Two oral drugs, brincidofovir and tecovirimat, have been approved for treatment of smallpox and have demonstrated efficacy against monkeypox in animals. Our aim was to describe the longitudinal clinical course of monkeypox in a high-income setting, coupled with viral dynamics, and any adverse events related to novel antiviral therapies. METHODS: In this retrospective observational study, we report the clinical features, longitudinal virological findings, and response to off-label antivirals in seven patients with monkeypox who were diagnosed in the UK between 2018 and 2021, identified through retrospective case-note review. This study included all patients who were managed in dedicated high consequence infectious diseases (HCID) centres in Liverpool, London, and Newcastle, coordinated via a national HCID network. FINDINGS: We reviewed all cases since the inception of the HCID (airborne) network between Aug 15, 2018, and Sept 10, 2021, identifying seven patients. Of the seven patients, four were men and three were women. Three acquired monkeypox in the UK: one patient was a health-care worker who acquired the virus nosocomially, and one patient who acquired the virus abroad transmitted it to an adult and child within their household cluster. Notable disease features included viraemia, prolonged monkeypox virus DNA detection in upper respiratory tract swabs, reactive low mood, and one patient had a monkeypox virus PCR-positive deep tissue abscess. Five patients spent more than 3 weeks (range 22-39 days) in isolation due to prolonged PCR positivity. Three patients were treated with brincidofovir (200 mg once a week orally), all of whom developed elevated liver enzymes resulting in cessation of therapy. One patient was treated with tecovirimat (600 mg twice daily for 2 weeks orally), experienced no adverse effects, and had a shorter duration of viral shedding and illness (10 days hospitalisation) compared with the other six patients. One patient experienced a mild relapse 6 weeks after hospital discharge. INTERPRETATION: Human monkeypox poses unique challenges, even to well resourced health-care systems with HCID networks. Prolonged upper respiratory tract viral DNA shedding after skin lesion resolution challenged current infection prevention and control guidance. There is an urgent need for prospective studies of antivirals for this disease. FUNDING: None.

Human immunodeficiency virus (HIV) in older people.

The number of older people living with human immunodeficiency virus (HIV) in the UK is rising. Older people are at risk of acquiring HIV infection for a multitude of reasons. This, combined with effective HIV treatment which has significantly prolonged life expectancy, means that health care professionals working in the UK can expect to see increasing numbers of older people with HIV infection. In this review article, we summarise the epidemiology of HIV amongst older people, including data from our local cohort in the city of Sheffield, UK. We discuss specific and practical issues in older patients including why older people are at risk, how to make a diagnosis and the importance of doing so early, guidelines for HIV testing and an update on anti-retroviral therapy including drug interactions and side effects.

Anakinra in the treatment of protracted paradoxical inflammatory reactions in HIV-associated tuberculosis in the United Kingdom: a report of two cases.

Paradoxical reactions, including immune reconstitution inflammatory syndrome (IRIS), are common in patients co-infected with human immunodeficiency virus (HIV) and tuberculosis (TB). Paradoxical reactions may confer substantial morbidity and mortality, especially in cases of central nervous system (CNS) TB, or through protracted usage of corticosteroids. No high-quality evidence is available to guide management in this scenario. Interleukin-1-mediated inflammation has been implicated in the pathophysiology of TB-IRIS. We describe two cases where anakinra (human recombinant interleukin-1 receptor antagonist) was used as steroid-sparing therapy for life-threatening protracted paradoxical inflammation in HIV-associated TB. In the first case of disseminated TB with lymphadenitis, protracted TB-IRIS led to amyloid A amyloidosis and nephrotic syndrome. In the second case of disseminated TB with cerebral tuberculomata, paradoxical inflammation caused unstable tuberculomata leading to profound neuro-disability. In both cases, paradoxical inflammation persisted for over a year. Protracted high-dose corticosteroid use led to adverse events yet failed to control inflammatory pathology. In both patients, anakinra successfully controlled paradoxical inflammation and facilitated withdrawal of corticosteroid therapy. Following anakinra therapy, nephrotic syndrome and neuro-disability resolved, respectively. Anakinra therapy for protracted paradoxical inflammation in HIV-associated TB may be a viable therapeutic option and warrants further research.

A unified personal protective equipment ensemble for clinical response to possible high consequence infectious diseases: A consensus document on behalf of the HCID programme.

The importance of appropriate personal protective equipment (PPE) as a component of healthcare worker (HCW) protection was highlighted during the Ebola virus disease (EVD) outbreak in West Africa. The large number of HCW deaths in Africa was in part due to lack of resources or prior training in PPE usage. As part of the Ebola legacy, the High Consequence Infectious Disease (HCID) programme was initiated by NHS England and Public Health England (PHE) to improve preparedness for Ebola and other infections that not only endanger the life of the patient, but also pose particular dangers to HCWs. A systematic review identified national standardisation of PPE protocols as a priority, but recognised that a lack of safety data limited the ability to mandate any one protocol. A simulation-based exercise was developed to assess the safety of PPE ensembles in use in the UK during first assessment of a patient with a possible HCID. A mannequin was adapted to expose volunteer HCWs to synthetic bodily fluids (vomit, sweat, diarrhoea and cough), each with a different coloured fluorescent tracer, invisible other than under ultraviolet (UV) light. After exposure, HCWs were examined under UV lights to locate fluorescent contamination, and were screened again after removing PPE (doffing) to detect any personal contamination. The exercise was videoed, allowing retrospective analysis of contamination events and user errors. The simulation testing identified significant HCW contamination events after doffing, related to protocol failure or complications in PPE doffing, providing conclusive evidence that improvements could be made. At a workshop with an expert stakeholder group, the data were examined and a unified PPE ensemble agreed. This ensemble was then tested in the same simulation exercise and no evidence of any HCW contamination was seen after doffing. Following further review by the working group, a consensus agreement has been reached and a unified 'HCID assessment PPE' ensemble, with accompanying donning and doffing protocols, is presented here.

Compliance with long-term malaria prophylaxis in British expatriates.

BACKGROUND: There were 219 million cases of malaria with 600,000 deaths in 2010. Current UK guidance recommends malaria chemoprophylaxis for travellers to malaria endemic areas. Despite proven efficacy, compliance amongst long-term travellers with prophylaxis and personal protective strategies is sub-optimal. This survey assesses compliance rates amongst Foreign and Commonwealth Office employees on placement in malaria endemic areas and establishes the rationale for their decisions. METHODS: A Survey Monkey questionnaire was circulated to Foreign and Commonwealth Office employees on long-term placement in endemic areas. This ascertained background knowledge of malaria, compliance with prevention strategies and the rationale for decisions made. RESULTS: The response rate was 56.5% (327 of 579); responses showed a good knowledge of malaria. 59% of respondents continued their prophylaxis for 0-3 months only. No pregnant women reported compliance of greater than 95%. More than half of the individuals with a compliance of <25% cited concerns about long term safety. 39.5% of respondents reported significant side-effects to chemoprophylaxis. 12.8% reported contracting malaria. CONCLUSION: Despite being well informed, poor adherence was reported, especially amongst pregnant respondents. The majority of individuals ceased medication within three months. Concern regarding the safety of long-term medication was the major barrier. Suggestions are made regarding optimisation of compliance or alternative strategies.

Hypoglycaemia associated with co-trimoxazole use in a 56-year-old Caucasian woman with renal impairment.

Here we present a case of refractory hypoglycaemia associated with use of the antibiotic trimethoprim-sulfamethoxazole (TMP-SMX). This was used to treat Pneumocystis jirovecii pneumonia (PCP) infection. The patient had significant pre-existing renal impairment with a kidney transplant in situ. Refractory hypoglycaemia occurred 5 days after starting the antibiotic and persisted for 36 h after its cessation. SMX contains the same sulphanilamide structural group as the oral hypoglycaemic agents called sulphonureas. SMX could therefore act as an insulin secretagogue. The inappropriately raised insulin and c-peptide levels seen in our patient support this theory. The 5-day asymptomatic period would allow sufficient time for the drug to accumulate and the extended period seen after its cessation would be seen in a dose-dependent side effect. Following 3 days of observation and continuous glycaemic support on the High Dependency Unit she was discharged back to the ward, with no further occurrence of hypoglycaemia.

Inhibition of macrophage apoptosis by Neisseria meningitidis requires nitric oxide detoxification mechanisms.

Host-driven macrophage apoptosis contributes to innate immunity during bacterial infection. Neisseria meningitidis inhibits apoptosis in a variety of cells, but its impact on macrophage apoptosis is unknown. We demonstrate that N. meningitidis prevents macrophage apoptosis via genes encoding nitric oxide detoxification and a porin, PorB.