Background Leprosy is rare in the United Kingdom (UK), but migration from endemic countries results in new cases being diagnosed each year. We documented the clinical presentation of leprosy in a ...non-endemic setting. Methods Demographic and clinical data on all new cases of leprosy managed in the Leprosy Clinic at the Hospital for Tropical Diseases, London between 1995 and 2018 were analysed. Results 157 individuals with a median age of 34 (range 13-85) years were included. 67.5% were male. Patients came from 34 different countries and most contracted leprosy before migrating to the UK. Eighty-two (51.6%) acquired the infection in India, Sri Lanka, Bangladesh, Nepal and Pakistan. 30 patients (19.1%) acquired leprosy in Africa, including 11 from Nigeria. Seven patients were born in Europe; three acquired their leprosy infection in Africa, three in South East Asia, and one in Europe. The mean interval between arrival in the UK and symptom onset was 5.87 years (SD 10.33), the longest time to diagnosis was 20 years. Borderline tuberculoid leprosy (n = 71, 42.0%), and lepromatous leprosy (n =, 53 33.1%) were the commonest Ridley Jopling types. Dermatologists were the specialists diagnosing leprosy most often. Individuals were treated with World Health Organization recommended drug regimens (rifampicin, dapsone and clofazimine). Conclusion Leprosy is not a disease of travellers but develops after residence in an leprosy endemic area. The number of individuals from a leprosy endemic country reflect both the leprosy prevalence and the migration rates to the United Kingdom. There are challenges in diagnosing leprosy in non-endemic areas and clinicians need to recognise the symptoms and signs of leprosy.
Abstract
Background
Treatment of hepatitis C (HCV) among people who inject drugs (PWID) is a critical component of efforts to eliminate viral hepatitis. A recent study found high HCV prevalence among ...PWID in two cities, Pretoria (84%) and Cape Town (44%). Very few (< 5%) HCV-infected individuals attended follow-up appointments. This sub-study explores differences between stated desire for cure and appointment attendance in light of perceived facilitators and barriers to HCV treatment and care access among PWID.
Method
Two sets of semi-structured interviews were implemented in a group of HCV-infected participants opportunistically sampled and recruited at harm reduction service sites. Initial interviews, conducted before the planned hospital appointment date, asked participants (
N
= 17, 9 in Pretoria and 8 in Cape Town) about past experiences of healthcare provision, plans to attend their referral appointment and perceived barriers and facilitators to seeking hepatitis treatment. Second interviews (
n
= 9, 4 in Pretoria, 5 in Cape Town), conducted after the planned referral appointment date, asked about appointment attendance and treatment experience. Trained social scientists with experience with PWID conducted the interviews which were recorded in detailed written notes. Data was thematically analysed in NVivo 11.
Results
Despite routine experiences of being stigmatised by the healthcare system in the past, most participants (
n
= 16, 94%) indicated a desire to attend their appointments. Attendance motivators included the desire to be cured, fear of dying and the wish to assist the research project. Perceived barriers to appointment attendance included fear of again experiencing stigmatisation and concerns about waiting periods and drug withdrawal. Perceived facilitators included the knowledge they would be treated quickly, and with respect and access to opioid substitution therapy. In the end, very few participants (
n
= 5) went to their appointment. Actual barriers to attendance included lack of finances, lack of urgency and forgetting and fatalism about dying.
Conclusions
South Africa can learn from other countries implementing HCV treatment for PWID. Successful linkage to care will require accessible, sensitive services where waiting time is limited. Psychosocial support prior to initiating referrals that focuses on building and maintaining a sense of self-worth and emphasising that delayed treatment hampers health outcomes is needed.
Dengue shock (DS) is the most severe complication of dengue infection; endothelial hyperpermeability leads to profound plasma leakage, hypovolaemia and extravascular fluid accumulation. At present, ...the only treatment is supportive with intravenous fluid, but targeted endothelial stabilising therapies and host immune modulators are needed. With the aim of prioritising potential therapeutics, we conducted a prospective observational study of adults (≥16 years) with DS in Vietnam from 2019-2022, comparing the pathophysiology underlying circulatory failure with patients with septic shock (SS), and investigating the association of biomarkers with clinical severity (SOFA score, ICU admission, mortality) and pulmonary vascular leak (daily lung ultrasound for interstitial and pleural fluid). Plasma was collected at enrolment, 48 hours later and hospital discharge. We measured biomarkers of inflammation (IL-6, ferritin), endothelial activation (Ang-1, Ang-2, sTie-2, VCAM-1) and endothelial glycocalyx breakdown (hyaluronan, heparan sulfate, endocan, syndecan-1). We enrolled 135 patients with DS (median age 26, median SOFA score 7, 34 required ICU admission, 5 deaths), together with 37 patients with SS and 25 healthy controls. Within the DS group, IL-6 and ferritin were associated with admission SOFA score (IL-6: βeta0.70, p<0.001 & ferritin: βeta0.45, p<0.001), ICU admission (IL-6: OR 2.6, p<0.001 & ferritin: OR 1.55, p<0.001) and mortality (IL-6: OR 4.49, p = 0.005 & ferritin: OR 13.8, p = 0.02); both biomarkers discriminated survivors and non-survivors at 48 hours and all patients who died from DS had pre-mortem ferritin ≥100,000ng/ml. IL-6 most strongly correlated with severity of pulmonary vascular leakage (R = 0.41, p<0.001). Ang-2 correlated with pulmonary vascular leak (R = 0.33, p<0.001) and associated with SOFA score (β 0.81, p<0.001) and mortality (OR 8.06, p = 0.002). Ang-1 was associated with ICU admission (OR 1.6, p = 0.005) and mortality (OR 3.62, p = 0.006). All 4 glycocalyx biomarkers were positively associated with SOFA score, but only syndecan-1 was associated with ICU admission (OR 2.02, p<0.001) and mortality (OR 6.51, p<0.001). This study highlights the central role of hyperinflammation in determining outcomes from DS; the data suggest that anti-IL-1 and anti-IL-6 immune modulators and Tie2 agonists may be considered as candidates for therapeutic trials in severe dengue.
Dengue is a mosquito-borne viral infection which has been estimated to cause a global economic burden of US$8.9 billion per year. 40% of this estimate was due to what are known as productivity costs ...(the costs associated with productivity loss from both paid and unpaid work that results from illness, treatment or premature death). Although productivity costs account for a significant proportion of the estimated economic burden of dengue, the methods used to calculate them are often very variable within health economic studies. The aim of this review was to systematically examine the current estimates of the productivity costs associated with dengue episodes in Asia and to increase awareness surrounding how productivity costs are estimated.
We searched PubMed and Web of Knowledge without date and language restrictions using terms related to dengue and cost and economics burden. The titles and abstracts of publications related to Asia were screened to identify relevant studies. The reported productivity losses and costs of non-fatal and fatal dengue episodes were then described and compared. Costs were adjusted for inflation to 2017 prices.
We reviewed 33 relevant articles, of which 20 studies reported the productivity losses, and 31 studies reported productivity costs. The productivity costs varied between US$6.7-1445.9 and US$3.8-1332 for hospitalized and outpatient non-fatal episodes, respectively. The productivity cost associated with fatal dengue episodes varied between US$12,035-1,453,237. A large degree of this variation was due to the range of different countries being investigated and their corresponding economic status. However, estimates for a given country still showed notable variation.
We found that the estimated productivity costs associated with dengue episodes in Asia are notable. However, owing to the significant variation in methodology and approaches applied, the reported productivity costs of dengue episodes were often not directly comparable across studies. More consistent and transparent methodology regarding the estimation of productivity costs would help the estimates of the economic burden of dengue be more accurate and comparable across studies.
In the Global South, young people who use drugs (YPWUD) are exposed to multiple interconnected social and health harms, with many low- and middle-income countries enforcing racist, ...prohibitionist-based drug policies that generate physical and structural violence. While harm reduction coverage for YPWUD is suboptimal globally, in low- and middle-income countries youth-focused harm reduction programs are particularly lacking. Those that do exist are often powerfully shaped by global health funding regimes that restrict progressive approaches and reach. In this commentary we highlight the efforts of young people, activists, allies, and organisations across some Global South settings to enact programs such as those focused on peer-to-peer information sharing and advocacy, overdose monitoring and response, and drug checking. We draw on our experiential knowledge and expertise to identify and discuss key challenges, opportunities, and recommendations for youth harm reduction movements, programs and practices in low- to middle-income countries and beyond, focusing on the need for youth-driven interventions. We conclude this commentary with several calls to action to advance harm reduction for YPWUD within and across Global South settings.
The presence of B-line artefacts, the main artefact reflecting lung abnormalities in dengue patients, is often assessed using lung ultrasound (LUS) imaging. Inspired by human visual attention that ...enables us to process videos efficiently by paying attention to where and when it is required, we propose a spatiotemporal attention mechanism for B-line detection in LUS videos. The spatial attention allows the model to focus on the most task relevant parts of the image by learning a saliency map. The temporal attention generates an attention score for each attended frame to identify the most relevant frames from an input video. Our model not only identifies videos where B-lines show, but also localizes, within those videos, B-line related features both spatially and temporally, despite being trained in a weakly-supervised manner. We evaluate our approach on a LUS video dataset collected from severe dengue patients in a resource-limited hospital, assessing the B-line detection rate and the model’s ability to localize discriminative B-line regions spatially and B-line frames temporally. Experimental results demonstrate the efficacy of our approach for classifying B-line videos with an F1 score of up to 83.2% and localizing the most salient B-line regions both spatially and temporally with a correlation coefficient of 0.67 and an IoU of 69.7%, respectively.
Dengue is a neglected tropical disease, for which no therapeutic agents have shown clinical efficacy to date. Clinical trials have used strikingly variable clinical endpoints, which hampers ...reproducibility and comparability of findings. We investigated a delta modified Sequential Organ Failure Assessment (delta mSOFA) score as a uniform composite clinical endpoint for use in clinical trials investigating therapeutics for moderate and severe dengue. We developed a modified SOFA score for dengue, measured and evaluated its performance at baseline and 48 h after enrolment in a prospective observational cohort of 124 adults admitted to a tertiary referral hospital in Vietnam with dengue shock. The modified SOFA score included pulse pressure in the cardiovascular component. Binary logistic regression, cox proportional hazard and linear regression models were used to estimate association between mSOFA, delta mSOFA and clinical outcomes. The analysis included 124 adults with dengue shock. 29 (23.4%) patients required ICU admission for organ support or due to persistent haemodynamic instability: 9/124 (7.3%) required mechanical ventilation, 8/124 (6.5%) required vasopressors, 6/124 (4.8%) required haemofiltration and 5/124 (4.0%) patients died. In univariate analyses, higher baseline and delta (48 h) mSOFA score for dengue were associated with admission to ICU, requirement for organ support and mortality, duration of ICU and hospital admission and IV fluid use. The baseline and delta mSOFA scores for dengue performed well to discriminate patients with dengue shock by clinical outcomes, including duration of ICU and hospital admission, requirement for organ support and death. We plan to use delta mSOFA as the primary endpoint in an upcoming host-directed therapeutic trial and investigate the performance of this score in other phenotypes of severe dengue in adults and children.
Dengue is the most common arboviral infection globally; a minority of patients develop shock due to profound plasma leak through a disrupted endothelial barrier. Understanding of the pathophysiology ...underlying plasma leak is incomplete, but emerging evidence indicates a key role for degradation of the endothelial glycocalyx.
We conducted an observational study in Vietnam to evaluate the sublingual microcirculation using sidestream darkfield imaging in (1) outpatients with confirmed dengue (2) patients hospitalized with dengue and (3) outpatients with other febrile illness (OFI). We estimated the glycocalyx degradation by measuring the perfused boundary region (PBR hf) and an overall microvascular health score (MVHS) with the software application GlycoCheck
at enrolment, 48 h later and hospital discharge/defervescence. We measured plasma syndecan1 and endocan at the same time-points. We compared PBR hf, MVHS, syndecan1 and endocan, between (1) outpatients with confirmed dengue vs. OFI and (2) patients with dengue subdivided by clinical severity of plasma leak.
We included 75 patients with dengue (41 outpatients, 15 inpatients, 19 in intensive care) and 12 outpatients with OFI. Images from 45 patients were analyzed using GlycoCheck
. There was no significant difference in PBR hf or MVHS between outpatients with dengue and OFI. Median plasma syndecan1 was not significantly different in outpatients with dengue vs. OFI, while median plasma endocan was significantly lower among patients with dengue vs. OFI during the critical phase. In patients with dengue, PBR hf was higher in patients with Grade 2 vs. Grade 0 plasma leakage during the critical phase (PBR hf 1.96 vs. 1.36 μm for Grade 2 vs. Grade 0 plasma leakage on days 4-6, respectively,
< 0.001). Median levels of plasma syndecan1 and endocan were higher in Grade 2 vs. Grade 0 plasma leakage, especially during the critical phase (Syndecan1 2,613.8 vs. 125.9 ng/ml for Grade 2 vs. Grade 0 plasma leakage on days 4-6, respectively,
< 0.001, and endocan 3.21 vs. 0.16 ng/ml for Grade 2 vs. Grade 0 plasma leakage on days 4-6, respectively).
We present the first human
evidence of glycocalyx disruption in dengue, with worse visual glycocalyx damage and higher plasma degradation products associated with more severe plasma leak.
All human cells are coated by a surface layer of proteoglycans, glycosaminoglycans (GAGs) and plasma proteins, called the glycocalyx. The glycocalyx transmits shear stress to the cytoskeleton of ...endothelial cells, maintains a selective permeability barrier, and modulates adhesion of blood leukocytes and platelets. Major components of the glycocalyx, including syndecans, heparan sulfate, and hyaluronan, are shed from the endothelial surface layer during conditions including ischaemia and hypoxia, sepsis, atherosclerosis, diabetes, renal disease, and some viral infections. Studying mechanisms of glycocalyx damage
can be challenging due to the complexity of immuno-inflammatory responses which are inextricably involved. Previously, both static as well as perfused
models have studied the glycocalyx, and have reported either imaging data, assessment of barrier function, or interactions of blood components with the endothelial monolayer. To date, no model has simultaneously incorporated all these features at once, however such a model would arguably enhance the study of vasculopathic processes. This review compiles a series of current
models described in the literature that have targeted the glycocalyx layer, their limitations, and potential opportunities for further developments in this field.
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