Publications by authors named "Nicky Longley"

Background: Immunocompromised travellers (ICTs) face greater infectious and non-infectious travel-associated risks than their immunocompetent counterparts. Increasing travel and emergence of novel immunosuppressants poses great challenges for travel medicine practitioners to confidently provide up-to-date evidence-based risk management advice and pre-travel care for ICTs.

Methods: We reviewed the records of ICTs attending the London Hospital for Tropical Diseases (HTD) Travel Clinic between 1st April 2019 and 30th April 2020 with the aim to describe demographic and travel characteristics, type, and severity of immunocompromise, the degree of risk associated with intended travel and evaluate travel advice.

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Hepatitis B virus (HBV) infection represents a significant global health threat, accounting for 300 million chronic infections and up to 1 million deaths each year. HBV disproportionately affects people who are under-served by health systems due to social exclusion, and can further amplify inequities through its impact on physical and mental health, relationship with stigma and discrimination, and economic costs. The 'inclusion health' agenda focuses on excluded and vulnerable populations, who often experience barriers to accessing healthcare, and are under-represented by research, resources, interventions, advocacy, and policy.

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In 2020, 21% of people who sought asylum in the UK were children. This population has complex interconnecting health and social needs. Assessment requires a holistic approach, with consideration of physical and mental health in addition to social and developmental well-being, within the whole family group.

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Asylum-seekers and refugees have an increased burden of infections compared with the general population. This has been widely recognised by countries welcoming those fleeing conflict and persecution; however, there are no screening standardised guidelines and regulatory processes. Identification of certain neglected tropical diseases (NTDs) and other infections is important for the health and well-being of the individual in addition to public health and biosecurity.

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Unaccompanied children (also called unaccompanied minors) are children who have been separated from both parents and other relatives and are not being cared for by an adult who, by law or custom, is responsible for doing so. From 2010 to 2020, unaccompanied minors accounted on average for 15.4% of the total number of first-time asylum applicants aged less than 18 years in the UK.

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The management of autoimmune, inflammatory diseases has been revolutionized by biologic therapies. A beneficial consequence of better disease control is that more patients are well enough to travel the world. There is now a class of traveller, the significantly immunosuppressed person with autoimmune disease, with specific risks and requirements.

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Objectives: The objective of this trial is to assess whether early antiviral therapy in outpatients with COVID-19 with either favipiravir plus lopinavir/ritonavir, lopinavir/ritonavir alone, or favipiravir alone, is associated with a decrease in viral load of SARS-CoV-2 compared with placebo.

Trial Design: FLARE is a phase IIA randomised, double-blind, 2x2 factorial placebo-controlled, interventional trial.

Participants: This trial is being conducted in the United Kingdom, with Royal Free Hospital, London as the lead site.

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Background: is the most common cause of meningitis in human immunodeficiency virus (HIV)-infected Africans. Despite universal exposure, only 5%-10% of patients with HIV/acquired immune deficiency syndrome and profound CD4 T-cell depletion develop disseminated cryptococcosis: host genetic factors may play a role. Prior targeted immunogenetic studies in cryptococcosis have comprised few Africans.

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Background: Determine TB-LAM is the first point-of-care test (POC) for HIV-associated tuberculosis (TB) and rapidly identifies TB in those at high-risk for short-term mortality. While the relationship between urine-LAM and mortality has been previously described, the outcomes of those undergoing urine-LAM testing have largely been assessed during short follow-up periods within diagnostic accuracy studies. We therefore sought to assess the relationship between baseline urine-LAM results and subsequent hospitalization and mortality under real-world conditions among outpatients in the first year of ART.

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Article Synopsis
  • * In a study of 43 patients, most were confirmed or probable COVID-19 cases, revealing five main categories of neurological disorders: encephalopathies, inflammatory central nervous system syndromes, ischemic strokes, peripheral neurological disorders, and other central disorders.
  • * Treatment outcomes varied, with many patients showing full or partial recovery, particularly those with encephalopathy and inflammatory CNS syndromes, while some experienced severe conditions like stroke or Guillain-Barré syndrome.
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Background: Screening for serum cryptococcal antigen (CrAg) may identify those at risk for disseminated cryptococcal disease (DCD), and preemptive fluconazole treatment may prevent progression to DCD. In August 2012, the Western Cape Province (WC), South Africa, adopted provider-initiated CrAg screening. We evaluated the implementation and effectiveness of this large-scale public-sector program during its first year, September 1, 2012-August 31, 2013.

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Background: Retrospective data suggest that cryptococcal antigen (CrAg) screening in patients with late-stage human immunodeficiency virus (HIV) initiating antiretroviral therapy (ART) may reduce cryptococcal disease and deaths. Prospective data are limited.

Methods: CrAg was measured using lateral flow assays (LFA) and latex agglutination (LA) tests in 645 HIV-positive, ART-naive patients with CD4 counts ≤100 cells/µL in Cape Town, South Africa.

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The contribution of fungal infections to the morbidity and mortality of HIV-infected individuals is largely unrecognized. A recent meeting highlighted several priorities that need to be urgently addressed, including improved epidemiological surveillance, increased availability of existing diagnostics and drugs, more training in the field of medical mycology, and better funding for research and provision of treatment, particularly in developing countries.

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Background:  Cryptococcal meningitis (CM) is a leading cause of death in individuals infected with human immunodeficiency virus (HIV). Identifying factors associated with mortality informs strategies to improve outcomes.

Methods:  Five hundred one patients with HIV-associated CM were followed prospectively for 10 weeks during trials in Thailand, Uganda, Malawi, and South Africa.

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Article Synopsis
  • The article reviews the risks and factors associated with cryptococcal immune reconstitution inflammatory syndrome (CM-IRIS) and highlights how understanding these can improve management and prevention strategies.
  • It identifies that low inflammatory response and CD4 cell count at the start, along with a fast immune recovery and high organism load, contribute to the occurrence of paradoxical CM-IRIS.
  • Recommendations include starting antifungal treatment early, timing ART carefully, and screening for cryptococcal antigen to prevent unmasking of CM-IRIS, which can lead to reduced mortality rates.
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HIV-associated cryptococcal meningitis (CM) is estimated to cause over half a million deaths annually in Africa. Many of these deaths are preventable. Screening patients for subclinical cryptococcal infection at the time of entry into antiretroviral therapy programs using cryptococcal antigen (CRAG) immunoassays is highly effective in identifying patients at risk of developing CM, allowing these patients to then be targeted with "preemptive" therapy to prevent the development of severe disease.

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Objective: To define more rapidly effective initial antifungal regimens sustainable in resource-constrained settings.

Methods: Cohort study in SW Uganda: Thirty HIV-seropositive, antiretroviral therapy-naïve, patients with first episode cryptococcal meningitis were treated with high dose fluconazole (1200 mg/d for 2 weeks, then 800 mg/d until ART started) plus amphotericin B (AmB, 1 mg/kg/d), with routine normal saline and potassium supplementation, for the initial 5 days. Outcome measures were early fungicidal activity (EFA), determined by serial quantitative CSF cultures, safety, and mortality.

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Background: Many deaths from cryptococcal meningitis (CM) may be preventable through early diagnosis and treatment. An inexpensive point-of-care (POC) assay for use with urine or a drop of blood would facilitate early diagnosis of cryptococcal infection in resource-limited settings. We compared cryptococcal antigen (CRAG) concentrations in plasma, serum, and urine from patients with CM, using an antigen-capture assay for glucuronoxylomannan (GXM) and a novel POC dipstick test.

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