Imperial College London

DrSophieYacoub

Faculty of MedicineDepartment of Infectious Disease

Honorary Clinical Research Fellow
 
 
 
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s.yacoub

 
 
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Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

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67 results found

Vuong NL, Cheung K-W, Periaswamy B, Vi TT, Duyen HTL, Leong YS, Binte Hamis ZN, Gregorova M, Ooi EE, Sessions O, Rivino L, Yacoub Set al., 2022, Hyperinflammatory syndrome, natural killer cell function and genetic polymorphisms in the pathogenesis of severe dengue., J Infect Dis

BACKGROUND: Severe dengue, characterized by shock and organ dysfunction is driven by an excessive host immune response. We investigated the role of hyperinflammation in dengue pathogenesis. METHODS: Patients recruited into an observational study were divided into three plasma leak severity grades. Hyperinflammatory biomarkers were measured at 4 time-points. Frequencies, activation and cytotoxic potential of NK cells were analysed by flow cytometry. RNA was extracted from sorted CD56+ NK cells and libraries prepared using SMART-Seq and sequenced using HiSeq3000 (Illumina). RESULTS: 69 patients were included (grade 0: 42, grade 1: 19, grade 2: 8 patients). Patients with grade 2 leakage had higher biomarkers than grade 0, including higher peak ferritin levels (83.3% vs 45.2%) and H scores (median 148.5 vs 105.5). NK cells from grade 2 patients exhibited decreased expression of perforin and granzyme B and activation markers. RNA sequencing revealed three SNPs in NK cell functional genes associated with more severe leakage; NK cell lectin-like receptor K1 gene (KLRK1) and PRF1 gene. CONCLUSIONS: Features of hyperinflammation are associated with dengue severity, including higher biomarkers, impaired NK cell function and polymorphisms in genes NK cell cytolyitc function genes (KLRK1 and PRF-1). Trials of immunomodulatory therapy in these patients is now warranted.

Journal article

Ming DK, Hernandez B, Sangkaew S, Vuong NL, Lam PK, Nguyet NM, Tam DTH, Trung DT, Tien NTH, Tuan NM, Chau NVV, Tam CT, Chanh HQ, Trieu HT, Simmons CP, Wills B, Georgiou P, Holmes AH, Yacoub Set al., 2022, Applied machine learning for the risk-stratification and clinical decision support of hospitalised patients with dengue in Vietnam, PLOS Digital Health, Vol: 1, Pages: e0000005-e0000005

BackgroundIdentifying patients at risk of dengue shock syndrome (DSS) is vital for effective healthcare delivery. This can be challenging in endemic settings because of high caseloads and limited resources. Machine learning models trained using clinical data could support decision-making in this context.MethodsWe developed supervised machine learning prediction models using pooled data from adult and paediatric patients hospitalised with dengue. Individuals from 5 prospective clinical studies in Ho Chi Minh City, Vietnam conducted between 12th April 2001 and 30th January 2018 were included. The outcome was onset of dengue shock syndrome during hospitalisation. Data underwent random stratified splitting at 80:20 ratio with the former used only for model development. Ten-fold cross-validation was used for hyperparameter optimisation and confidence intervals derived from percentile bootstrapping. Optimised models were evaluated against the hold-out set.FindingsThe final dataset included 4,131 patients (477 adults and 3,654 children). DSS was experienced by 222 (5.4%) of individuals. Predictors were age, sex, weight, day of illness at hospitalisation, indices of haematocrit and platelets over first 48 hours of admission and before the onset of DSS. An artificial neural network model (ANN) model had best performance with an area under receiver operator curve (AUROC) of 0.83 (95% confidence interval [CI], 0.76–0.85) in predicting DSS. When evaluated against the independent hold-out set this calibrated model exhibited an AUROC of 0.82, specificity of 0.84, sensitivity of 0.66, positive predictive value of 0.18 and negative predictive value of 0.98.InterpretationThe study demonstrates additional insights can be obtained from basic healthcare data, when applied through a machine learning framework. The high negative predictive value could support interventions such as early discharge or ambulatory patient management in this population. Work is underway to incorporate t

Journal article

Kerdegari H, Phung NTH, McBride A, Pisani L, Nguyen HV, Duong TB, Razavi R, Thwaites L, Yacoub S, Gomez Aet al., 2021, B-Line Detection and Localization in Lung Ultrasound Videos Using Spatiotemporal Attention, APPLIED SCIENCES-BASEL, Vol: 11

Journal article

Choisy M, McBride A, Chambers M, Ho Quang C, Nguyen Quang H, Xuan Chau NT, Thi GN, Bonell A, Evans M, Ming D, Ngo-Duc T, Quang Thai P, Dang Giang DH, Dan Thanh HN, Ngoc Nhung H, Lowe R, Maude R, Elyazar I, Surendra H, Ashley EA, Thwaites L, van Doorn HR, Kestelyn E, Dondorp AM, Thwaites G, Vinh Chau NV, Yacoub Set al., 2021, Climate change and health in Southeast Asia – defining research priorities and the role of the Wellcome Trust Africa Asia Programmes, Wellcome Open Research, Vol: 6, Pages: 278-278

<ns4:p>This article summarises a recent virtual meeting organised by the Oxford University Clinical Research Unit in Vietnam on the topic of climate change and health, bringing local partners, faculty and external collaborators together from across the Wellcome and Oxford networks. Attendees included invited local and global climate scientists, clinicians, modelers, epidemiologists and community engagement practitioners, with a view to setting priorities, identifying synergies and fostering collaborations to help define the regional climate and health research agenda. In this summary paper, we outline the major themes and topics that were identified and what will be needed to take forward this research for the next decade. We aim to take a broad, collaborative approach to including climate science in our current portfolio where it touches on infectious diseases now, and more broadly in our future research directions. We will focus on strengthening our research portfolio on climate-sensitive diseases, and supplement this with high quality data obtained from internal studies and external collaborations, obtained by multiple methods, ranging from traditional epidemiology to innovative technology and artificial intelligence and community-led research. Through timely agenda setting and involvement of local stakeholders, we aim to help support and shape research into global heating and health in the region.</ns4:p>

Journal article

Pley C, Evans M, Lowe R, Montgomery H, Yacoub Set al., 2021, Digital and technological innovation in vector-borne disease surveillance to predict, detect, and control climate-driven outbreaks, LANCET PLANETARY HEALTH, Vol: 5, Pages: E739-E745

Journal article

Kartsonaki C, 2021, Characteristics and outcomes of an international cohort of 400,000 hospitalised patients with Covid-19

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Policymakers need robust data to respond to the COVID-19 pandemic. We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, the world’s largest international, standardised cohort of hospitalised patients.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>The dataset analysed includes COVID-19 patients hospitalised between January 2020 and May 2021. We investigated how symptoms on admission, comorbidities, risk factors, and treatments varied by age, sex, and other characteristics. We used Cox proportional hazards models to investigate associations between demographics, symptoms, comorbidities, and other factors with risk of death, admission to intensive care unit (ICU), and invasive mechanical ventilation (IMV).</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>439,922 patients with laboratory-confirmed (91.7%) or clinically-diagnosed (8.3%) SARS-CoV-2 infection from 49 countries were enrolled. Age (adjusted hazard ratio [HR] per 10 years 1.49 [95% CI 1.49-1.50]) and male sex (1.26 [1.24-1.28]) were associated with a higher risk of death. Rates of admission to ICU and use of IMV increased with age up to age 60, then dropped. Symptoms, comorbidities, and treatments varied by age and had varied associations with clinical outcomes. Tuberculosis was associated with an 86% higher risk of death, and HIV with an 87% higher risk of death. Case fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients.</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>The size of our international database and the standardized da

Journal article

Sangkaew S, Ming D, Boonyasiri A, Honeyford K, Kalayanarooj S, Yacoub S, Dorigatti I, Holmes Aet al., 2021, Risk predictors of progression to severe disease during the febrile phase of dengue: a systematic review and meta-analysis, Lancet Infectious Diseases, Vol: 21, Pages: 1014-1026, ISSN: 1473-3099

BACKGROUND: The ability to accurately predict early progression of dengue to severe disease is crucial for patient triage and clinical management. Previous systematic reviews and meta-analyses have found significant heterogeneity in predictors of severe disease due to large variation in these factors during the time course of the illness. We aimed to identify factors associated with progression to severe dengue disease that are detectable specifically in the febrile phase. METHODS: We did a systematic review and meta-analysis to identify predictors identifiable during the febrile phase associated with progression to severe disease defined according to WHO criteria. Eight medical databases were searched for studies published from Jan 1, 1997, to Jan 31, 2020. Original clinical studies in English assessing the association of factors detected during the febrile phase with progression to severe dengue were selected and assessed by three reviewers, with discrepancies resolved by consensus. Meta-analyses were done using random-effects models to estimate pooled effect sizes. Only predictors reported in at least four studies were included in the meta-analyses. Heterogeneity was assessed using the Cochrane Q and I2 statistics, and publication bias was assessed by Egger's test. We did subgroup analyses of studies with children and adults. The study is registered with PROSPERO, CRD42018093363. FINDINGS: Of 6643 studies identified, 150 articles were included in the systematic review, and 122 articles comprising 25 potential predictors were included in the meta-analyses. Female patients had a higher risk of severe dengue than male patients in the main analysis (2674 [16·2%] of 16 481 vs 3052 [10·5%] of 29 142; odds ratio [OR] 1·13 [95% CI 1·01-1·26) but not in the subgroup analysis of studies with children. Pre-existing comorbidities associated with severe disease were diabetes (135 [31·3%] of 431 with vs 868 [16·0%] of 5421 witho

Journal article

McBride A, Mehta P, Rivino L, Ramanan A, Yacoub Set al., 2021, Targeting hyperinflammation in infection: can we harness the COVID-19 therapeutics momentum to end the dengue drugs drought? Comment, LANCET MICROBE, Vol: 2, Pages: E277-E278

Journal article

ISARIC Clinical Characterisation Group, 2021, COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study, Infection: journal of infectious disease, Vol: 49, Pages: 899-905, ISSN: 0300-8126

BACKGROUND: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. METHODS: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. RESULTS: 'Typical' symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. INTERPRETATION: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men.

Journal article

Nguyen LV, Phung KL, Ming DKY, Huynh TLD, Nguyet MN, Dong THT, Kien DTH, Chau NVV, Chanpheaktra N, Lum LCS, Pleites E, Simmons CP, Rosenberger KD, Jaenisch T, Bell D, Acestor N, Halleux C, Olliaro PL, Wills BA, Geskus RB, Yacoub Set al., 2021, Combination of inflammatory and vascular markers in the febrile phase of dengue is associated with more severe outcomes, eLife, Vol: 10, ISSN: 2050-084X

Background:Early identification of severe dengue patients is important regarding patient management and resource allocation. We investigated the association of 10 biomarkers (VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, CRP) with the development of severe/moderate dengue (S/MD).Methods:We performed a nested case-control study from a multi-country study. A total of 281 S/MD and 556 uncomplicated dengue cases were included.Results:On days 1–3 from symptom onset, higher levels of any biomarker increased the risk of developing S/MD. When assessing together, SDC-1 and IL-1RA were stable, while IP-10 changed the association from positive to negative; others showed weaker associations. The best combinations associated with S/MD comprised IL-1RA, Ang-2, IL-8, ferritin, IP-10, and SDC-1 for children, and SDC-1, IL-8, ferritin, sTREM-1, IL-1RA, IP-10, and sCD163 for adults.Conclusions:Our findings assist the development of biomarker panels for clinical use and could improve triage and risk prediction in dengue patients.Funding:This study was supported by the EU's Seventh Framework Programme (FP7-281803 IDAMS), the WHO, and the Bill and Melinda Gates Foundation.

Journal article

Nguyen LV, Nguyen THQ, Nguyen THT, Nguyen MT, Duong THK, Phung KL, Dong THT, Tran VN, Yacoub S, Jaenisch T, Geskus RB, Simmons CP, Wills BAet al., 2021, Higher Plasma Viremia in the Febrile Phase Is Associated With Adverse Dengue Outcomes Irrespective of Infecting Serotype or Host Immune Status: An Analysis of 5642 Vietnamese Cases, CLINICAL INFECTIOUS DISEASES, Vol: 72, Pages: E1074-E1083, ISSN: 1058-4838

Journal article

Li Bassi G, Suen JY, Dalton HJ, White N, Shrapnel S, Fanning JP, Liquet B, Hinton S, Vuorinen A, Booth G, Millar JE, Forsyth S, Panigada M, Laffey J, Brodie D, Fan E, Torres A, Chiumello D, Corley A, Elhazmi A, Hodgson C, Ichiba S, Luna C, Murthy S, Nichol A, Ng PY, Ogino M, Pesenti A, Huynh TT, Fraser JFet al., 2021, An appraisal of respiratory system compliance in mechanically ventilated covid-19 patients, CRITICAL CARE, Vol: 25, ISSN: 1364-8535

Journal article

Pham QT, Rabaa MA, Duong HL, Dang QT, Tran DQ, Ha-Linh Q, Ngoc-Anh HT, Phung CD, Ngu DN, Tran AT, La NQ, Tran MP, Vinh C, Nguyen CK, Dang DA, Tran ND, Thwaites G, Doorn HRV, Marc Cet al., 2021, The First 100 Days of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Control in Vietnam, CLINICAL INFECTIOUS DISEASES, Vol: 72, Pages: E334-E342, ISSN: 1058-4838

Journal article

Haymet AB, Bartnikowski N, Wood ES, Vallely MP, McBride A, Yacoub S, Biering SB, Harris E, Suen JY, Fraser JFet al., 2021, Studying the Endothelial Glycocalyx in vitro: What Is Missing?, FRONTIERS IN CARDIOVASCULAR MEDICINE, Vol: 8, ISSN: 2297-055X

Journal article

Vuong NL, Lam PK, Ming DKY, Duyen HTL, Nguyen NM, Tam DTH, Kien DTH, Chau NVV, Chanpheaktra N, Lum LCS, Pleités E, Simmons CP, Rosenberger K, Jaenisch T, Bell D, Acestor N, Halleux C, Olliaro PL, Wills BA, Geskus RB, Yacoub Set al., 2021, Combination of inflammatory and vascular markers in the febrile phase of dengue is associated with more severe outcomes

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Early identification of severe dengue patients is important regarding patient management and resource allocation. We investigated the association of ten biomarkers (VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, CRP) with the development of severe/moderate dengue (S/MD).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We performed a nested case-control study from a multi-country study. A total of 281 S/MD and 556 uncomplicated dengue cases were included.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>On days 1-3 from symptom onset, higher levels of any biomarker increased the risk of developing S/MD. When assessing together, SDC-1 and IL-1RA were stable, while IP-10 changed the association from positive to negative; others showed weaker associations. The best combinations associated with S/MD comprised IL-1RA, Ang-2, IL-8, ferritin, IP-10, and SDC-1 for children, and SDC-1, IL-8, ferritin, sTREM-1, IL-1RA, IP-10, and sCD163 for adults.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Our findings assist the development of biomarker panels for clinical use and could improve triage and risk prediction in dengue patients.</jats:p></jats:sec><jats:sec><jats:title>Summary of the main point</jats:title><jats:p>Higher levels of any of VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, and CRP on illness days 1-3 increased the risk of developing severe/moderate dengue. The relationships differed between children and adults and some changed when assessed together.</jats:p></jats:sec>

Journal article

Chau NVV, Hai HB, Greeff H, Phan Nguyen Quoc K, Trieu HT, Khoa LDV, Nguyen CN, Van HMT, Yen LM, Tan LV, Dung NT, Clifton D, Yacoub S, Thwaites CLet al., 2021, Wearable remote monitoring for patients with COVID-19 in low-resource settings: case study, BMJ Innovations, Vol: 7, Pages: s12-s15, ISSN: 2055-8074

Journal article

McBride A, Chanh HQ, Fraser JF, Yacoub S, Obonyo NGet al., 2020, Microvascular dysfunction in septic and dengue shock: Pathophysiology and implications for clinical management., Glob Cardiol Sci Pract, Vol: 2020, ISSN: 2305-7823

The microcirculation comprising of arterioles, capillaries and post-capillary venules is the terminal vascular network of the systemic circulation. Microvascular homeostasis, comprising of a balance between vasoconstriction, vasodilation and endothelial permeability in healthy states, regulates tissue perfusion. In severe infections, systemic inflammation occurs irrespective of the infecting microorganism(s), resulting in microcirculatory dysregulation and dysfunction, which impairs tissue perfusion and often precedes end-organ failure. The common hallmarks of microvascular dysfunction in both septic shock and dengue shock, are endothelial cell activation, glycocalyx degradation and plasma leak through a disrupted endothelial barrier. Microvascular tone is also impaired by a reduced bioavailability of nitric oxide. In vitro and in vivo studies have however demonstrated that the nature and extent of microvascular dysfunction as well as responses to volume expansion resuscitation differ in these two clinical syndromes. This review compares and contrasts the pathophysiology of microcirculatory dysfunction in septic versus dengue shock and the attendant effects of fluid administration during resuscitation.

Journal article

Nguyen VVC, Vo TL, Nguyen TD, Lam MY, Ngo NQM, Le MH, Nghiem MN, Nguyen TD, Dinh NHM, Lam AN, Le THN, Le NTN, Nguyen THN, Nguyen TTH, Kestelyn E, Nguyen TPD, Tran CX, Tran TH, Nguyen TP, Tran NHT, Geskus RB, Tran TT, Nguyen TT, Nguyen TB, Tang CT, Thwaites G, Le VTet al., 2020, The Natural History and Transmission Potential of Asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infection, CLINICAL INFECTIOUS DISEASES, Vol: 71, Pages: 2679-2687, ISSN: 1058-4838

Journal article

Zellweger RM, Yacoub S, Chan YFZ, Soon D, Shafi H, Ooi ST, Chan M, Jacobson L, Sessions OM, Vincent A, Low JGH, Ooi EE, Wang L, Wijaya L, Tan Ket al., 2020, Disentangling etiologies of CNS infections in Singapore using multiple correspondence analysis and random forest, SCIENTIFIC REPORTS, Vol: 10, ISSN: 2045-2322

Journal article

Phung KL, McBride A, Duyen HTL, Trieu TH, Vink H, Wills B, Yacoub Set al., 2020, Visual and Biochemical Evidence of Glycocalyx Disruption in Human Dengue Infection, and Association With Plasma Leakage Severity, FRONTIERS IN MEDICINE, Vol: 7

Journal article

Gan ES, Tan HC, Duyen HTL, Trieu TH, Wills B, Seidah NG, Ooi EE, Yacoub Set al., 2020, Dengue virus induces PCSK9 expression to alter antiviral responses and disease outcomes, JOURNAL OF CLINICAL INVESTIGATION, Vol: 130, Pages: 5223-5234, ISSN: 0021-9738

Journal article

Sanz MG, De Sario V, Garcia-Mingo A, Nolder D, Dawood N, Alvarez-Martinez MJ, Daly R, Lowe P, Yacoub S, Moore DAJ, Chiodini PLet al., 2020, Chagas disease in the United Kingdom: A review of cases at the Hospital for Tropical Diseases London 1995-2018. The current state of detection of Chagas disease in the UK, TRAVEL MEDICINE AND INFECTIOUS DISEASE, Vol: 36, ISSN: 1477-8939

Journal article

Ming DK, Sorawat S, Chanh HQ, Nhat PTH, Yacoub S, Georgiou P, Holmes AHet al., 2020, Continuous physiological monitoring using wearable technology to inform individual management of infectious diseases, public health and outbreak responses, International Journal of Infectious Diseases, Vol: 96, Pages: 648-654, ISSN: 1201-9712

Optimal management of infectious diseases is guided by up-to-date information at the individual and public health level. For infections of global importance including emerging pandemics such as COVID-19 or prevalent endemic diseases such like dengue, identifying patients at risk of severe disease and clinical deterioration can be challenging given the majority present with a mild illness. In our article, we describe the use of wearable technology for continuous physiological monitoring in healthcare. Deployment of wearables in hospital settings for the management of infectious diseases, or in the community to support syndromic surveillance during outbreaks could provide significant, cost effective advantages and improve healthcare delivery. We highlight a range of promising technologies employed by wearable devices and discuss the technical and ethical issues relating to implementation in the clinic, with specific focus on low- and middle- income countries. Finally, we propose a set of essential criteria for the roll-out of wearable technology for clinical use.

Journal article

Gallagher P, Chan KR, Rivino L, Yacoub Set al., 2020, The association of obesity and severe dengue: possible pathophysiological mechanisms, JOURNAL OF INFECTION, Vol: 81, Pages: 10-16, ISSN: 0163-4453

Journal article

Redoni M, Yacoub S, Rivino L, Giacobbe DR, Luzzati R, Di Bella Set al., 2020, Dengue: Status of current and under-development vaccines, REVIEWS IN MEDICAL VIROLOGY, Vol: 30, ISSN: 1052-9276

Journal article

Nguyen LV, Huynh TLD, Phung KL, Dong THT, Nguyen VVC, Nguyen VK, Chanpheaktra N, Lum LCS, Pleites E, Jones NK, Simmons CP, Rosenberger K, Jaenisch T, Halleux C, Olliaro PL, Wills B, Yacoub Set al., 2020, C-reactive protein as a potential biomarker for disease progression in dengue: a multi-country observational study, BMC MEDICINE, Vol: 18, ISSN: 1741-7015

Journal article

Yacoub S, Nguyen NM, Chanh HQ, Tam DTH, Vuong NL, Chau NTX, Phong NT, Trieu HT, Luong Thi Hue T, Cao Thi T, Dinh The T, Duyen HTL, Van NTT, Nguyen Than Ha Q, Rivino L, Gallagher P, Jones NK, Geskus RB, Kestelyn Eet al., 2020, Metformin as adjunctive therapy for dengue in overweight and obese patients: A protocol for an open-label clinical trial (MeDO), Wellcome Open Research, Vol: 5

Background: Dengue is a disease of major global importance. While most symptomatic infections are mild, a small proportion of patients progress to severe disease with risk of hypovolaemic shock, organ dysfunction and death. In the absence of effective antiviral or disease modifying drugs, clinical management is solely reliant on supportive measures. Obesity is a growing problem among young people in Vietnam and is increasingly recognised as an important risk factor for severe dengue, likely due to alterations in host immune and inflammatory pathways. Metformin, a widely used anti-hyperglycaemic agent with excellent safety profile, has demonstrated potential as a dengue therapeutic in vitro and in a retrospective observational study of adult dengue patients with type 2 diabetes. This study aims to assess the safety and tolerability of metformin treatment in overweight and obese dengue patients, and investigate its effects on several clinical, immunological and virological markers of disease severity. Methods: This open label trial of 120 obese/overweight dengue patients will be performed in two phases, with a metformin dose escalation if no safety concerns arise in phase one. The primary endpoint is identification of clinical and laboratory adverse events. Sixty overweight and obese dengue patients aged 10-30 years will be enrolled at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam. Participants will complete a 5-day course of metformin therapy and be compared to a non-treated group of 60 age-matched overweight and obese dengue patients. Discussion: Previously observed antiviral and immunomodulatory effects of metformin make it a promising dengue therapeutic candidate in appropriately selected patients. This study will assess the safety and tolerability of adjunctive metformin in the management of overweight and obese young dengue patients, as well as its effects on markers of viral replication, endothelial dysfunction and host immune responses. Trial

Journal article

Nguyen NM, Chanh HQ, Tam DTH, Vuong NL, Chau NTX, Chau NVV, Phong NT, Trieu HT, Luong Thi Hue T, Cao Thi T, Dinh The T, Duyen HTL, Van NTT, Nguyen Than Ha Q, Rivino L, Gallagher P, Jones NK, Geskus RB, Kestelyn E, Yacoub Set al., 2020, Metformin as adjunctive therapy for dengue in overweight and obese patients: a protocol for an open-label clinical trial (MeDO)., Wellcome Open Res, Vol: 5, ISSN: 2398-502X

Background:  Dengue is a disease of major global importance. While most symptomatic infections are mild, a small proportion of patients progress to severe disease with risk of hypovolaemic shock, organ dysfunction and death.  In the absence of effective antiviral or disease modifying drugs, clinical management is solely reliant on supportive measures. Obesity is a growing problem among young people in Vietnam and is increasingly recognised as an important risk factor for severe dengue, likely due to alterations in host immune and inflammatory pathways. Metformin, a widely used anti-hyperglycaemic agent with excellent safety profile, has demonstrated potential as a dengue therapeutic in vitro and in a retrospective observational study of adult dengue patients with type 2 diabetes.  This study aims to assess the safety and tolerability of metformin treatment in overweight and obese dengue patients, and investigate its effects on several clinical, immunological and virological markers of disease severity. Methods: This open label trial of 120 obese/overweight dengue patients will be performed in two phases, with a metformin dose escalation if no safety concerns arise in phase one. The primary endpoint is identification of clinical and laboratory adverse events.  Sixty overweight and obese dengue patients aged 10-30 years will be enrolled at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam. Participants will complete a 5-day course of metformin therapy and be compared to a non-treated group of 60 age-matched overweight and obese dengue patients. Discussion:  Previously observed antiviral and immunomodulatory effects of metformin make it a promising dengue therapeutic candidate in appropriately selected patients. This study will assess the safety and tolerability of adjunctive metformin in the management of overweight and obese young dengue patients, as well as its effects on markers of viral replication, endothelial dysfunction an

Journal article

Gan P, Yacoub S, 2019, Picturing health: dengue in Vietnam, LANCET, Vol: 394, Pages: 2059-2066, ISSN: 0140-6736

Journal article

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