41 results found
Gan ES, Tan HC, Le DHT, et al., 2020, Dengue virus induces PCSK9 expression to alter antiviral responses and disease outcomes., J Clin Invest
Dengue virus (DENV) infection requires cholesterol as a proviral factor, although statin treatment did not show antiviral efficacy in patients with dengue. Here, we show that DENV infection manipulated cholesterol metabolism in cells residing in low-oxygen microenvironments (hypoxia) such as in the liver, spleen, and lymph nodes. DENV infection induced expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), which reduces low-density lipoprotein receptor (LDLR) recycling and hence cholesterol uptake. We found that, whereas LDLR uptake would have distributed cholesterol throughout the various cell compartments, de novo cholesterol synthesis enriched this lipid in the endoplasmic reticulum (ER). With cholesterol enrichment in the ER, ER-resident STING and type I IFN (IFN) activation was repressed during DENV infection. Our in vitro findings were further supported by the detection of elevated plasma PCSK9 levels in patients with dengue with high viremia and increased severity of plasma leakage. Our findings therefore suggest that PCSK9 plays a hitherto unrecognized role in dengue pathogenesis and that PCSK9 inhibitors could be a suitable host-directed treatment for patients with dengue.
Redoni M, Yacoub S, Rivino L, et al., 2020, Dengue: Status of current and under-development vaccines, REVIEWS IN MEDICAL VIROLOGY, Vol: 30, ISSN: 1052-9276
Nguyen LV, Huynh TLD, Phung KL, et 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
Gan P, Yacoub S, 2019, Picturing health: dengue in Vietnam, LANCET, Vol: 394, Pages: 2059-2066, ISSN: 0140-6736
Hung TM, Wills B, Clapham HE, et al., 2019, The uncertainty surrounding the burden of post-acute consequences of dengue infection, Trends in Parasitology, Vol: 35, Pages: 673-676, ISSN: 0169-4758
Post-acute consequences currently form a significant component of the dengue disability-adjusted life year (DALY) burden estimates. However, there is considerable uncertainty regarding the incidence, duration, and severity of these symptoms. Further research is needed to more accurately estimate the health and economic burden of these dengue manifestations.
Turner HC, Nguyen VH, Yacoub S, et al., 2019, Achieving affordable critical care in low-income and middle-income countries, BMJ Global Health, Vol: 4, Pages: 1-4, ISSN: 2059-7908
Whitehorn J, Yacoub S, 2019, Global warming and arboviral infections, CLINICAL MEDICINE, Vol: 19, Pages: 149-152, ISSN: 1470-2118
Rodriguez-Manzano J, Chia PY, Yeo TW, et al., 2018, Improving Dengue Diagnostics and Management Through Innovative Technology (vol 20, 25, 2018), CURRENT INFECTIOUS DISEASE REPORTS, Vol: 20, ISSN: 1523-3847
Rodriguez-Manzano J, Ying Chia P, Wen Yeo T, et al., 2018, Improving Dengue diagnostics and management through innovative technology, Current Infectious Disease Reports, Vol: 20, ISSN: 1534-3146
Purpose of Review:Dengue continues to be a major global public health threat. Symptomatic infections can cause a spectrum of disease ranging from a mild febrile illness to severe and potentially life-threatening manifestations. Management relies on supportive treatment with careful fluid replacement. The purpose of this review is to define the unmet needs and challenges in current dengue diagnostics and patient monitoring and outline potential novel technologies to address these needs.Recent Findings:There have been recent advances in molecular and point-of-care (POC) diagnostics as well as technologies including wireless communication, low-power microelectronics, and wearable sensors that have opened up new possibilities for management, clinical monitoring, and real-time surveillance of dengue.Summary:Novel platforms utilizing innovative technologies for POC dengue diagnostics and wearable patient monitors have the potential to revolutionize dengue surveillance, outbreak response, and management at population and individual levels. Validation studies of these technologies are urgently required in dengue-endemic areas.
Morra ME, Altibi AMA, Iqtadar S, et al., 2018, Definitions for warning signs and signs of severe dengue according to the WHO 2009 classification: Systematic review of literature, REVIEWS IN MEDICAL VIROLOGY, Vol: 28, ISSN: 1052-9276
Nguyen THM, Nguyen HP, Ho DTN, et al., 2018, Dengue-Associated Posterior Reversible Encephalopathy Syndrome, Vietnam, EMERGING INFECTIOUS DISEASES, Vol: 24, Pages: 402-404, ISSN: 1080-6040
Yacoub S, Trieu HT, Phung KL, et al., 2017, Cardio-haemodynamic assessment and venous lactate in severe dengue: Relationship with recurrent shock and respiratory distress, PLOS NEGLECTED TROPICAL DISEASES, Vol: 11, ISSN: 1935-2735
BackgroundDengue can cause plasma leakage that may lead to dengue shock syndrome (DSS). In approximately 30% of DSS cases, recurrent episodes of shock occur. These patients have a higher risk of fluid overload, respiratory distress and poor outcomes. We investigated the association of echocardiographically-derived cardiac function and intravascular volume parameters plus lactate levels, with the outcomes of recurrent shock and respiratory distress in severe dengue.Methods/Principle findingsWe performed a prospective observational study in Paediatric and adult ICU, at the Hospital for Tropical Diseases (HTD), Ho Chi Minh City, Vietnam. Patients with dengue were enrolled within 12 hours of admission to paediatric or adult ICU. A haemodynamic assessment and portable echocardiograms were carried out daily for 5 days from enrolment and all interventions recorded.102 patients were enrolled; 22 patients did not develop DSS, 48 had a single episode of shock and 32 had recurrent shock. Patients with recurrent shock had a higher enrolment pulse than those with 1 episode or no shock (median: 114 vs. 100 vs. 100 b/min, P = 0.002), significantly lower Stroke Volume Index (SVI), (median: 21.6 vs. 22.8 vs. 26.8mls/m2, P<0.001) and higher lactate levels (4.2 vs. 2.9 vs. 2.2 mmol/l, P = 0.001). Higher SVI and worse left ventricular function (higher Left Myocardial Performance Index) on study days 3–5 was associated with the secondary endpoint of respiratory distress. There was an association between the total IV fluid administered during the ICU admission and respiratory distress (OR: 1.03, 95% CI 1.01–1.06, P = 0.001). Admission lactate levels predicted patients who subsequently developed recurrent shock (P = 0.004), and correlated positively with the total IV fluid volume received (rho: 0.323, P = 0.001) and also with admission ALT (rho: 0.764, P<0.001) and AST (rho: 0.773, P<0.001).Conclusions/SignificanceEcho-derived intravascular volume assessment and venou
Yacoub S, Lam PK, Huynh TT, et al., 2017, Endothelial nitric oxide pathways in the pathophysiology of dengue: a prospective observational study., Clinical Infectious Diseases, Vol: 65, Pages: 1453-1461, ISSN: 1058-4838
Background: Dengue can cause increased vascular permeability that may lead to hypovolemic shock. Endothelial dysfunction may underlie this; however the association of endothelial nitric oxide pathways with disease severity is unknown. Methods: We performed a prospective observational study in two Vietnamese hospitals, assessing patients presenting early (<72 hours fever) and patients hospitalized with warning signs or severe dengue. The reactive hyperaemic index (RHI), which measures endothelium-dependent vasodilation and is a surrogate marker of endothelial function and NO bioavailability was evaluated using peripheral artery tonometry (EndoPAT) and plasma levels of L-arginine, Arginase-1 and ADMA were measured at serial time-points. The main outcome of interest was plasma leakage severity. Results: 314 patients were enrolled, median age of the participants was 21 (IQR 13-30) years. No difference was found in the endothelial parameters between dengue and other febrile illness (OFI). Considering dengue patients, the RHI was significantly lower for patients with severe plasma leakage compared to those with no leakage (1.46 vs. 2.00, P<0.001), over acute time-points, apparent already in the early febrile phase (1.29 vs. 1.75, P=0.012). RHI correlated negatively with arginase-1, and positively with L-arginine (P=0.001). Endothelial dysfunction/NO bioavailability is associated with worse plasma leakage, occurs early in dengue illness and correlates with hypoargininaemia and high arginase-1 levels.
Yacoub S, Lam PK, Vu LH, et al., 2016, Association of microvascular function and endothelial biomarkers with clinical outcome in dengue: an observational study, Journal of Infectious Diseases, Vol: 214, Pages: 697-706, ISSN: 1537-6613
Background. The hallmark of severe dengue is increased microvascular permeability however alterations in the microcirculation and their evolution over the course of dengue are unknown.Methods. We conducted a prospective observational study to evaluate the sublingual microcirculation using sidestream dark field imaging in patients presenting early (<72 hours fever) and patients hospitalized with warning signs or severe dengue in Vietnam. Clinical, microvascular function, global haemodynamics assessed by echocardiograms and serological markers of endothelial activation were performed at 4 time points.Results. 165 patients were enrolled. No difference was found between the microcirculatory parameters comparing dengue with other febrile illnesses. Proportion of perfused vessels (PPV) and Mean Flow Index (MFI) were lower in dengue patients with plasma leakage (PPV: 88.1% vs. 90.6%, P=0.010 and MFI: 2.1 vs. 2.4, P=0.007) most marked during the critical phase. PPV and MFI correlated with the endothelial activation markers, VCAM-1 (P<0.001 for both) and Angiopoietin-2 (P<0.001 and P=0.001 respectively) with a negative association.Conclusion. Modest microcirculatory alterations occur in dengue, are associated with plasma leakage and correlate with molecules of endothelial activation, Angiopoietin-2 and VCAM-1.
Jaenisch T, Dong THT, Nguyen TTK, et al., 2016, Clinical evaluation of dengue and identification of risk factors for severe disease: protocol for a multicentre study in 8 countries, BMC Infectious Diseases, Vol: 16, ISSN: 1471-2334
Nguyen VVC, Le BC, Desquesnes M, et al., 2016, A Clinical and Epidemiological Investigation of the First Reported Human Infection With the Zoonotic Parasite Trypanosoma evansi in Southeast Asia, Clinical Infectious Diseases, Vol: 62, Pages: 1002-1008, ISSN: 1537-6591
Background. Trypanosoma is a genus of unicellular parasitic flagellate protozoa. Trypanosoma brucei species and Trypanosoma cruzi are the major agents of human trypanosomiasis; other Trypanosoma species can cause human disease, but are rare. In March 2015, a 38-year-old woman presented to a healthcare facility in southern Vietnam with fever, headache, and arthralgia. Microscopic examination of blood revealed infection with Trypanosoma.Methods. Microscopic observation, polymerase chain reaction (PCR) amplification of blood samples, and serological testing were performed to identify the infecting species. The patient's blood was screened for the trypanocidal protein apolipoprotein L1 (APOL1), and a field investigation was performed to identify the zoonotic source.Results. PCR amplification and serological testing identified the infecting species as Trypanosoma evansi. Despite relapsing 6 weeks after completing amphotericin B therapy, the patient made a complete recovery after 5 weeks of suramin. The patient was found to have 2 wild-type APOL1 alleles and a normal serum APOL1 concentration. After responsive animal sampling in the presumed location of exposure, cattle and/or buffalo were determined to be the most likely source of the infection, with 14 of 30 (47%) animal blood samples testing PCR positive for T. evansi.Conclusions. We report the first laboratory-confirmed case of T. evansi in a previously healthy individual without APOL1 deficiency, potentially contracted via a wound while butchering raw beef, and successfully treated with suramin. A linked epidemiological investigation revealed widespread and previously unidentified burden of T. evansi in local cattle, highlighting the need for surveillance of this infection in animals and the possibility of further human cases.
Yacoub S, Mongkolsapaya J, Screaton G, 2016, Recent advances in understanding dengue, F1000 Research, Vol: 5, ISSN: 2046-1402
Vannucchi V, Tomberli B, Zammarchi L, et al., 2015, Chagas disease as a cause of heart failure and ventricular arrhythmias in patients long removed from endemic areas: an emerging problem in Europe, JOURNAL OF CARDIOVASCULAR MEDICINE, Vol: 16, Pages: 817-823, ISSN: 1558-2027
Screaton G, Mongkolsapaya J, Yacoub S, et al., 2015, New insights into the immunopathology and control of dengue virus infection, Nature Reviews Immunology, Vol: 15, Pages: 745-759, ISSN: 1474-1741
Dengue virus poses a major threat to global public health: two-thirds of the world's population is now at risk from infection by this mosquito-borne virus. Dengue virus causes a range of diseases with a small proportion of infected patients developing severe plasma leakage that leads to dengue shock syndrome, organ impairment and bleeding. Infection with one of the four viral serotypes results in the development of homotypic immunity to that serotype. However, subsequent infection with a different serotype is associated with an increased risk of developing severe disease, which has led to the suggestion that severe disease is triggered by immunopathology. This Review outlines recent advances in the understanding of immunopathology, vaccine development and human monoclonal antibodies produced against dengue virus.
Taylor WR, Fox A, Khuong TP, et al., 2015, Dengue in Adults Admitted to a Referral Hospital in Hanoi, Vietnam, AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, Vol: 92, Pages: 1141-1149, ISSN: 0002-9637
Thuy DB, Oanh KNP, Duong HTH, et al., 2015, A pregnant woman with acute cardiorespiratory failure: dengue myocarditis, LANCET, Vol: 385, Pages: 1260-1260, ISSN: 0140-6736
Yacoub S, Wertheim H, Simmons CP, et al., 2015, Microvascular and endothelial function for risk prediction in dengue: an observational study, LANCET, Vol: 385, Pages: 102-102, ISSN: 0140-6736
Yacoub S, Wills B, 2015, Dengue: an update for clinicians working in non-endemic areas, CLINICAL MEDICINE, Vol: 15, Pages: 82-85, ISSN: 1470-2118
Yacoub S, Wills B, 2014, Predicting outcome from dengue, BMC MEDICINE, Vol: 12, ISSN: 1741-7015
Whitehorn J, Yacoub S, Anders KL, et al., 2014, Dengue Therapeutics, Chemoprophylaxis, and Allied Tools: State of the Art and Future Directions, PLOS NEGLECTED TROPICAL DISEASES, Vol: 8, ISSN: 1935-2735
Yacoub S, Wertheim H, Simmons CP, et al., 2014, Cardiovascular manifestations of the emerging dengue pandemic, NATURE REVIEWS CARDIOLOGY, Vol: 11, Pages: 335-345, ISSN: 1759-5002
Yacoub S, Mongkolsapaya J, Screaton G, 2013, The pathogenesis of dengue, CURRENT OPINION IN INFECTIOUS DISEASES, Vol: 26, Pages: 284-289, ISSN: 0951-7375
Yacoub S, Grifiths A, Chau TTH, et al., 2012, Cardiac function and haemodynamics in Vietnemese patients with different dengue severity grades, INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, Vol: 16, Pages: E119-E119, ISSN: 1201-9712
Yacoub S, Griffiths A, Tran THC, et al., 2012, Cardiac function in Vietnamese patients with different dengue severity grades, CRITICAL CARE MEDICINE, Vol: 40, Pages: 477-483, ISSN: 0090-3493
Yacoub S, Kotit S, Yacoub MH, 2011, Disease appearance and evolution against a background of climate change and reduced resources, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES, Vol: 369, Pages: 1719-1729, ISSN: 1364-503X
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.