PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-11 (11)
 

Clipboard (0)
None

Select a Filter Below

Journals
Year of Publication
1.  The Association of Cytokines with Severe Dengue in Children 
Tropical Medicine and Health  2014;42(4):137-144.
Background: Dengue virus infection is a major public health problem. A hypothesis put forward for severe dengue is the cytokine storm, a sudden increase in cytokines that induces vascular permeability. Previous studies and our recent meta-analysis showed that IL-6, IL-8, IFNγ, TNFα, VEGF-A and VCAM-1 are associated with dengue shock syndrome. Therefore, in this study we aim to validate the association of these cytokines with severe dengue.
Methods & Findings: In a hospital based-case control study in Vietnam, children with dengue fever, other febrile illness and healthy controls were recruited. Dengue virus infection was confirmed by several diagnostic tests. Multiplex immunoassay using Luminex technology was used to measure cytokines simultaneously. A positive association with dengue shock syndrome was found for VCAM-1, whereas a negative association was found for IFNγ. Furthermore, multivariate logistic analysis also showed that VCAM-1 and IFNγ were independently correlated with dengue shock syndrome.
Conclusion: IFNγ and VCAM-1 were associated with dengue shock syndrome, although their role in the severe dengue pathogenesis remains unclear. Additional studies are required to shed further light on the function of these cytokines in severe dengue.
doi:10.2149/tmh.2014-09
PMCID: PMC4253061  PMID: 25589878
Association; cytokine; dengue; severity; shock
2.  Development of clinical decision rules to predict recurrent shock in dengue 
Critical Care  2013;17(6):R280.
Introduction
Mortality from dengue infection is mostly due to shock. Among dengue patients with shock, approximately 30% have recurrent shock that requires a treatment change. Here, we report development of a clinical rule for use during a patient’s first shock episode to predict a recurrent shock episode.
Methods
The study was conducted in Center for Preventive Medicine in Vinh Long province and the Children’s Hospital No. 2 in Ho Chi Minh City, Vietnam. We included 444 dengue patients with shock, 126 of whom had recurrent shock (28%). Univariate and multivariate analyses and a preprocessing method were used to evaluate and select 14 clinical and laboratory signs recorded at shock onset. Five variables (admission day, purpura/ecchymosis, ascites/pleural effusion, blood platelet count and pulse pressure) were finally trained and validated by a 10-fold validation strategy with 10 times of repetition, using a logistic regression model.
Results
The results showed that shorter admission day (fewer days prior to admission), purpura/ecchymosis, ascites/pleural effusion, low platelet count and narrow pulse pressure were independently associated with recurrent shock. Our logistic prediction model was capable of predicting recurrent shock when compared to the null method (P < 0.05) and was not outperformed by other prediction models. Our final scoring rule provided relatively good accuracy (AUC, 0.73; sensitivity and specificity, 68%). Score points derived from the logistic prediction model revealed identical accuracy with AUCs at 0.73. Using a cutoff value greater than −154.5, our simple scoring rule showed a sensitivity of 68.3% and a specificity of 68.2%.
Conclusions
Our simple clinical rule is not to replace clinical judgment, but to help clinicians predict recurrent shock during a patient’s first dengue shock episode.
doi:10.1186/cc13135
PMCID: PMC4057383  PMID: 24295509
3.  Community-Based Control of Aedes aegypti By Using Mesocyclops in Southern Vietnam 
We previously reported a new community-based mosquito control strategy that resulted in elimination of Aedes aegypti (Linn.) in 40 of 46 communes in northern and central Vietnam, and with annual recurrent total costs (direct and indirect) of only $0.28–$0.89 international dollars per person. This control strategy was extended to four provinces in southern Vietnam in Long An and Hau Giang (2004–2007) and to Long An, Ben Tre, and Vinh Long (2005–2010). In a total of 14 communes with 124,743 residents, the mean ± SD of adult female Ae. aegypti was reduced from 0.93 ± 0.62 to 0.06 ± 0.09, and the reduction of immature Ae. aegypti averaged 98.8%. By the final survey, no adults could be collected in 6 of 14 communes, and one commune, Binh Thanh, also had no immature forms. Although the community-based programs also involved community education and clean-up campaigns, the prevalence of Mesocyclops in large water storage containers > 50 liters increased from 12.77 ± 8.39 to 75.69 ± 9.17% over periods of 15–45 months. At the conclusion of the study, no confirmed dengue cases were detected in four of the five communes for which diagnostic serologic analysis was performed. The rate of progress was faster in communes that were added in stages to the program but the reason for this finding was unclear. At the completion of the formal project, sustainability funds were set up to provide each commune with the financial means to ensure that community-based dengue control activities continued.
doi:10.4269/ajtmh.2012.11-0466
PMCID: PMC3335693  PMID: 22556087
4.  The origin and phylogeography of dog rabies virus 
The Journal of General Virology  2008;89(Pt 11):2673-2681.
Rabies is a progressively fatal and incurable viral encephalitis caused by a lyssavirus infection. Almost all of the 55 000 annual rabies deaths in humans result from infection with dog rabies viruses (RABV). Despite the importance of rabies for human health, little is known about the spread of RABV in dog populations, and patterns of biodiversity have only been studied in limited geographical space. To address these questions on a global scale, we sequenced 62 new isolates and performed an extensive comparative analysis of RABV gene sequence data, representing 192 isolates sampled from 55 countries. From this, we identified six clades of RABV in non-flying mammals, each of which has a distinct geographical distribution, most likely reflecting major physical barriers to gene flow. Indeed, a detailed analysis of phylogeographic structure revealed only limited viral movement among geographical localities. Using Bayesian coalescent methods we also reveal that the sampled lineages of canid RABV derive from a common ancestor that originated within the past 1500 years. Additionally, we found no evidence for either positive selection or widespread population bottlenecks during the global expansion of canid RABV. Overall, our study reveals that the stochastic processes of genetic drift and population subdivision are the most important factors shaping the global phylogeography of canid RABV.
doi:10.1099/vir.0.2008/003913-0
PMCID: PMC3326349  PMID: 18931062
5.  Association of Mast Cell-Derived VEGF and Proteases in Dengue Shock Syndrome 
Background
Recent in-vitro studies have suggested that mast cells are involved in Dengue virus infection. To clarify the role of mast cells in the development of clinical Dengue fever, we compared the plasma levels of several mast cell-derived mediators (vascular endothelial cell growth factor [VEGF], soluble VEGF receptors [sVEGFRs], tryptase, and chymase) and -related cytokines (IL-4, -9, and -17) between patients with differing severity of Dengue fever and healthy controls.
Methodology/Principal Findings
The study was performed at Children's Hospital No. 2, Ho Chi Minh City, and Vinh Long Province Hospital, Vietnam from 2002 to 2005. Study patients included 103 with Dengue fever (DF), Dengue hemorrhagic fever (DHF), and Dengue shock syndrome (DSS), as diagnosed by the World Health Organization criteria. There were 189 healthy subjects, and 19 febrile illness patients of the same Kinh ethnicity. The levels of mast cell-derived mediators and -related cytokines in plasma were measured by ELISA. VEGF and sVEGFR-1 levels were significantly increased in DHF and DSS compared with those of DF and controls, whereas sVEGFR-2 levels were significantly decreased in DHF and DSS. Significant increases in tryptase and chymase levels, which were accompanied by high IL-9 and -17 concentrations, were detected in DHF and DSS patients. By day 4 of admission, VEGF, sVEGFRs, and proteases levels had returned to similar levels as DF and controls. In-vitro VEGF production by mast cells was examined in KU812 and HMC-1 cells, and was found to be highest when the cells were inoculated with Dengue virus and human Dengue virus-immune serum in the presence of IL-9.
Conclusions
As mast cells are an important source of VEGF, tryptase, and chymase, our findings suggest that mast cell activation and mast cell-derived mediators participate in the development of DHF. The two proteases, particularly chymase, might serve as good predictive markers of Dengue disease severity.
Author Summary
To clarify the involvement of mast cells in the development of severe Dengue diseases, plasma levels of mast cell-derived mediators, namely vascular endothelial cell growth factor (VEGF), tryptase, and chymase, were estimated in Dengue patients and control subjects in Vietnam. The levels of the mediators were significantly increased in Dengue hemorrhagic fever (DHF) and Dengue shock syndrome (DSS) patients compared with those of Dengue fever (DF) and control (febrile illness and healthy subjects) patients, and the soluble form of VEGF receptors (sVEGFR)-1 and -2 levels were significantly changed in the patients with severe disease. After 2–4 days of admission, the mediator levels had returned to similar levels as those of DF and control subjects. Furthermore, the levels of the Th17 cell-derived mast-cell activators IL-9 and -17 were increased in DHF and DSS. In-vitro production of VEGF in human mast cells was significantly enhanced in the presence of IL-9 when these cells were inoculated with Dengue virus in the presence of human Dengue virus-immune serum. As mast cells are an important source of VEGF, and tryptase and chymase are considered to be specific markers for mast cell activation, mast cells and mast cell-derived mediators might participate in the development of DHF/DSS.
doi:10.1371/journal.pntd.0001505
PMCID: PMC3283553  PMID: 22363824
6.  Elevated Levels of Cell-Free Circulating DNA in Patients with Acute Dengue Virus Infection 
PLoS ONE  2011;6(10):e25969.
Background
Apoptosis is thought to play a role in the pathogenesis of severe dengue and the release of cell-free DNA into the circulatory system in several medical conditions. Therefore, we investigated circulating DNA as a potential biomarker for severe dengue.
Methods and Findings
A direct fluorometric degradation assay using PicoGreen was performed to quantify cell-free DNA from patient plasma. Circulating DNA levels were significantly higher in patients with dengue virus infection than with other febrile illnesses and healthy controls. Remarkably, the increase of DNA levels correlated with the severity of dengue. Additionally, multivariate logistic regression analysis showed that circulating DNA levels independently correlated with dengue shock syndrome.
Conclusions
Circulating DNA levels were increased in dengue patients and correlated with dengue severity. Additional studies are required to show the benefits of this biomarker in early dengue diagnosis and for the prognosis of shock complication.
doi:10.1371/journal.pone.0025969
PMCID: PMC3189230  PMID: 22016795
10.  Hemorrhagic Fever with Renal Syndrome, Vietnam 
Emerging Infectious Diseases  2010;16(2):363-365.
doi:10.3201/eid1602.091204
PMCID: PMC2958020  PMID: 20113591
Hantavirus infection; Seoul virus; hemorrhagic fever with renal syndrome; virus; Vietnam; letter
11.  Protective and Enhancing HLA Alleles, HLA-DRB1*0901 and HLA-A*24, for Severe Forms of Dengue Virus Infection, Dengue Hemorrhagic Fever and Dengue Shock Syndrome 
Background
Dengue virus (DV) infection is one of the most important mosquito-borne diseases in the tropics. Recently, the severe forms, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), have become the leading cause of death among children in Southern Vietnam. Protective and/or pathogenic T cell immunity is supposed to be important in the pathogenesis of DHF and DSS.
Methodology/Principal Findings
To identify HLA alleles controlling T cell immunity against dengue virus (DV), we performed a hospital-based case control study at Children's Hospital No.2, Ho Chi Minh City (HCMC), and Vinh Long Province Hospital (VL) in Southern Vietnam from 2002 to 2005. A total of 211 and 418 patients with DHF and DSS, respectively, diagnosed according to the World Health Organization (WHO) criteria, were analyzed for their characteristic HLA-A, -B and -DRB1 alleles. Four hundred fifty healthy children (250 from HCMC and 200 from VL) of the same Kinh ethnicity were also analyzed as population background. In HLA class I, frequency of the HLA-A*24 showed increased tendency in both DHF and DSS patients, which reproduced a previous study. The frequency of A*24 with histidine at codon 70 (A*2402/03/10), based on main anchor binding site specificity analysis in DSS and DHF patients, was significantly higher than that in the population background groups (HCMC 02-03 DSS: OR = 1.89, P = 0.008, DHF: OR = 1.75, P = 0.033; VL 02-03 DSS: OR = 1.70, P = 0.03, DHF: OR = 1.46, P = 0.38; VL 04-05 DSS: OR = 2.09, P = 0.0075, DHF: OR = 2.02, P = 0.038). In HLA class II, the HLA-DRB1*0901 frequency was significantly decreased in secondary infection of DSS in VL 04-05 (OR = 0.35, P = 0.0025, Pc = 0.03). Moreover, the frequency of HLA-DRB1*0901 in particular was significantly decreased in DSS when compared with DHF in DEN-2 infection (P = 0.02).
Conclusion
This study improves our understanding of the risk of HLA-class I for severe outcome of DV infection in the light of peptide anchor binding site and provides novel evidence that HLA-class II may control disease severity (DHF to DSS) in DV infection.
Author Summary
Dengue has become one of the most common viral diseases transmitted by infected mosquitoes (with any of the four dengue virus serotypes: DEN-1, -2, -3, or -4). It may present as asymptomatic or illness, ranging from mild to severe disease. Recently, the severe forms, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), have become the leading cause of death among children in Southern Vietnam. The pathogenesis of DHF/DSS, however, is not yet completely understood. The immune response, virus virulence, and host genetic background are considered to be risk factors contributing to disease severity. Human leucocyte antigens (HLA) expressed on the cell surface function as antigen presenting molecules and those polymorphism can change individuals' immune response. We investigated the HLA-A, -B (class I), and -DRB1 (class II) polymorphism in Vietnamese children with different severity (DHF/DSS) by a hospital-based case-control study. The study showed persons carrying HLA-A*2402/03/10 are about 2 times more likely to have severe dengue infection than others. On the other hand, HLA-DRB1*0901 persons are less likely to develop DSS with DEN-2 virus infection. These results clearly demonstrated that HLA controlled the susceptibility to severe forms of DV infection.
doi:10.1371/journal.pntd.0000304
PMCID: PMC2553281  PMID: 18827882

Results 1-11 (11)