Pathogenesis of Haemorrhage Associated With Dengue Infection in Adults in Vietnam

Clinical experience suggests that adults with dengue manifest a pattern of complications different from those observed in children, but direct comparisons among populations experiencing the same exposure have rarely been published. I conducted a large prospective descriptive study of dengue across all age-groups presenting to a single institution in an endemic country during a defined time-period. Vascular leakage was more severe in the paediatric patients and DSS developed much more frequently in this age-group. In contrast haemorrhagic manifestations and severe organ involvement were more common in adults. Similar to the established findings in children, typical coagulation abnormalities were apparent in the adults - i.e. prolonged APTT with reduced fibrinogen levels but without evidence of true disseminated intravascular coagulation. However thrombocytopenia was significantly worse among the adults throughout the evolution of the disease, even after adjusting for the higher rate of secondary infections in this group, and platelet counts after recovery remained lower than in the children. Clinically severe liver involvement was seen only in adults and was infrequent but usually resulted in severe bleeding. Chronic hepatitis B co-infection was associated with modestly but significantly increased levels of alanine aminotransferase, but did not otherwise impact the clinical picture. To investigate the mechanisms underlying the increase in APTT I carried out APTT Mixing Studies confirming that deficiency of coagulation factors is a major contributory factor. Since there is little evidence for procoagulant activation the most likely mechanism for this would be leakage of coagulation proteins, many of which are of a similar size to albumin. An additional explanation for the increased APTT could be the presence of a circulating anticoagulant. I found very high levels of heparan sulfate (HS) in the dengue plasma, but was not able to show that the HS exerts an anticoagulant effect. I also used FACS analysis to demonstrate that circulating endothelial cells (CECs) are increased during dengue infections and that percentage CECs correlate with the severity of the coagulopathy and with bleeding. Parallel increases in both CECs and HS levels support the theory that disruption of the endothelial cell/glycocalyx complex occurs during dengue infections - i.e. CECs appear to be shed from the endothelial layer while HS may be shed from the surface glycocalyx. These disruptions likely affect the function of the complex and could contribute to the pathogenesis of the systemic vascular leak syndrome

Biocontrol of Alternaria alternata YZU, a causal of stem end rot disease on pitaya, with soil phosphate solubilizing bacteria

Stem end rot is the most destructive disease caused by Alternaria alternata YZU in pitaya-growing regions of Vietnam. This study was conducted to characterize antagonistic phosphate-solubilizing bacteria (PSB) from rhizosphere soil for their biocontrol activities against A. alternata YZU and evaluate the effect of temperature, pH, and water activity on that antagonism. Among seven PSB isolated from 45 rhizosphere soil samples, PSB31 (identified as Bacillus sp. strain IMAU61039, Accession number: MF803700.1) exhibited the highest antagonistic activity against A. alternata YZU with an average inhibition diameter of 0.65 ± 0.05 cm. The results also show that the strain PSB31 controlled the mycelial growth of A. alternata YZU by secreting antifungal metabolites. The most potent inhibitory activity was identified under in vitro conditions of 25 °C, pH 7, and aw 1. The isolated PSB31 could be a potential biological control agent against A. alternata YZU

Liver Involvement Associated with Dengue Infection in Adults in Vietnam

Globally, the number of adults hospitalized with dengue has increased markedly in recent years. It has been suggested that hepatic dysfunction is more significant in this group than among children. We describe the spectrum and evolution of disease manifestations among 644 adults with dengue who were prospectively recruited on admission to a major infectious disease hospital in southern Vietnam and compare them with a group of patients with similar illnesses not caused by dengue. Transaminase levels increased in virtually all dengue patients and correlated with other markers of disease severity. However, peak enzyme values usually occurred later than other complications. Clinically severe liver involvement was infrequent and idiosyncratic, but usually resulted in severe bleeding. Chronic co-infection with hepatitis B was associated with modestly but significantly increased levels of alanine aminotransferase, but did not otherwise impact the clinical picture

Clinical Features of Dengue in a Large Vietnamese Cohort: Intrinsically Lower Platelet Counts and Greater Risk for Bleeding in Adults than Children

Dengue is a common and potentially serious viral illness. Complications include plasma leakage from small blood vessels causing shock and dysfunction of the systems that control blood clotting, resulting in bleeding. The disease used to affect children predominantly, but in recent years, the number of adult patients has been increasing. As there is limited data describing the patterns of complications by age, we performed this study to compare clinical and laboratory features, management, and outcomes of the disease for over 1,500 children and adults with confirmed dengue recruited at the same time at a single hospital in the Southern Vietnam. We found that plasma leakage and shock were more common and severe in children than adults, while bleeding and organ dysfunction were more frequent in adults. Adults had lower platelet counts throughout the illness course as well as at a follow-up visit several weeks after recovery. Platelets are a crucial element in controlling bleeding, and the intrinsically lower counts in adults compared to children may contribute to the greater risk for bleeding in this patient group. Knowledge about differences in the patterns of dengue-related complications between children and adults should help clinicians to diagnose and treat patients more effectively

Diagnostic Accuracy of NS1 ELISA and Lateral Flow Rapid Tests for Dengue Sensitivity, Specificity and Relationship to Viraemia and Antibody Responses

Dengue is a viral infection of humans that is transmitted by mosquitoes. Dengue is a very important public health problem in many developing countries. Recently, new tests to help diagnose patients with dengue have been developed. Evaluating these tests to see how well they perform in different countries and in different health care settings is an important process that helps to guide health care policy on whether these assays are likely to be useful in making a diagnosis, and if so, when best to use them. Our hospital-based results, using two different types of NS1 tests for diagnosing dengue, indicates that these tests are most sensitive when used during the first 3 days of illness and are most likely to be positive if the patient has primary dengue. Our results also show that a positive NS1 test result is a reflection of the amount of virus in the blood, so that patients with high amounts of virus in the blood are more likely to be NS1 positive. Collectively, the results indicate these NS1 tests deserve inclusion in the diagnostic approach to dengue

A modified Sequential Organ Failure Assessment score for dengue: development, evaluation and proposal for use in clinical trials

Background 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. Methods 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. Results 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. Conclusions 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

Effectiveness of perindopril/amlodipine fixed-dose combination in the treatment of hypertension: a systematic review

Background: Uncontrolled blood pressure is a major risk factor for cardiovascular diseases. Fixed-dose combination (FDC) therapy offers a promising approach to addressing this challenge by providing a convenient single-tablet solution that enhances the effectiveness of blood pressure control. In our systematic review, we assess the effectiveness of perindopril/amlodipine FDC in managing blood pressure.Methods: We conducted a comprehensive search across four primary electronic databases, namely, PubMed, Virtual Health Library (VHL), Global Health Library (GHL), and Google Scholar, as of 8 February 2022. Additionally, we performed a manual search to find relevant articles. The quality of the selected articles was evaluated using the Study Quality Assessment Tools (SQAT) checklist from the National Institute of Health and the ROB2 tool from Cochrane.Results: Our systematic review included 17 eligible articles. The findings show that the use of perindopril/amlodipine FDC significantly lowers blood pressure and enhances the quality of blood pressure control. Compared to the comparison group, the perindopril/amlodipine combination tablet resulted in a higher rate of blood pressure response and normalization. Importantly, perindopril/amlodipine FDC contributes to improved patient adherence with minimal side effects. However, studies conducted to date have not provided assessments of the cost-effectiveness of perindopril/amlodipine FDC.Conclusion: In summary, our analysis confirms the effectiveness of perindopril/amlodipine FDC in lowering blood pressure, with combination therapy outperforming monotherapy and placebo. Although mild adverse reactions were observed in a small subset of participants, cost-effectiveness assessments for this treatment remain lacking in the literature

Performance Evaluation of Relay Selection Schemes in Beacon-Assisted Dual-Hop Cognitive Radio Wireless Sensor Networks under Impact of Hardware Noises

To solve the problem of energy constraints and spectrum scarcity for cognitive radio wireless sensor networks (CR-WSNs), an underlay decode-and-forward relaying scheme is considered, where the energy constrained secondary source and relay nodes are capable of harvesting energy from a multi-antenna power beacon (PB) and using that harvested energy to forward the source information to the destination. Based on the time switching receiver architecture, three relaying protocols, namely, hybrid partial relay selection (H-PRS), conventional opportunistic relay selection (C-ORS), and best opportunistic relay selection (B-ORS) protocols are considered to enhance the end-to-end performance under the joint impact of maximal interference constraint and transceiver hardware impairments. For performance evaluation and comparison, we derive the exact and asymptotic closed-form expressions of outage probability (OP) and throughput (TP) to provide significant insights into the impact of our proposed protocols on the system performance over Rayleigh fading channel. Finally, simulation results validate the theoretical results