Overview of latest articles and publications on ebola in PubMed. PubMed is a service of the US National Library of Medicine that includes over 18 million citations from MEDLINE and other life science journals.
- Assessment of changes of vector borne diseases with wetland characteristics using multivariate analysis.
Sheela AM, Sarun S, Justus J, et al. Assessment of changes of vector borne diseases with wetland characteristics using multivariate analysis. [JOURNAL ARTICLE]Environ Geochem Health 2014 Nov 21.Vector borne diseases are a threat to human health. Little attention has been paid to the prevention of these diseases. We attempted to identify the significant wetland characteristics associated with the spread of chikungunya, dengue fever and malaria in Kerala, a tropical region of South West India using multivariate analyses (hierarchical cluster analysis, factor analysis and multiple regression). High/medium turbid coastal lagoons and inland water-logged wetlands with aquatic vegetation have significant effect on the incidence of chikungunya while dengue influenced by high turbid coastal beaches and malaria by medium turbid coastal beaches. The high turbidity in water is due to the urban waste discharge namely sewage, sullage and garbage from the densely populated cities and towns. The large extent of wetland is low land area favours the occurrence of vector borne diseases. Hence the provision of pollution control measures at source including soil erosion control measures is vital. The identification of vulnerable zones favouring the vector borne diseases will help the authorities to control pollution especially from urban areas and prevent these vector borne diseases. Future research should cover land use cover changes, climatic factors, seasonal variations in weather and pollution factors favouring the occurrence of vector borne diseases.
- Dengue fever in a liver-transplanted patient: a case report.
Weerakkody RM, Palangasinghe DR, Dalpatadu KP, et al. Dengue fever in a liver-transplanted patient: a case report. [JOURNAL ARTICLE]J Med Case Rep 2014 Nov 21; 8(1):378.Dengue fever is one of the commonest mosquito-borne diseases in the tropics, and Sri Lanka is no exception. Despite its commonness, dengue fever has rarely been described among patients who have undergone transplantation. We report the case of a patient with dengue fever after liver transplantation, which, to the best of our knowledge, is the first such reported case outside Brazil.Our patient was a 46-year-old Sri Lakan man who presented to our institution two years after undergoing an ABO-compatible cadaveric liver transplant. At presentation, he had typical symptoms of dengue fever. He was taking prednisolone 5mg daily and tacrolimus 3mg twice daily as immunosuppression. Initial investigations showed thrombocytopenia and neutropenia that reached a nadir by day 7 of his illness. He had elevated liver enzymes as well. The diagnosis was confirmed on the basis of NS1 antigen detection by enzyme-linked immunosorbent assay. His blood cultures and polymerase chain reaction tests for cytomegalovirus were negative. He made an uneventful recovery and was discharged by day 9 of his illness. However, normalization of liver function took nearly two weeks. In three previously reported Brazilian cases of dengue after liver transplantation, the patients presented with dengue shock syndrome, in contrast to the relatively milder presentation of our patient. Because of the lack of case reports in the literature, it is difficult to ascertain the risk factors for severe dengue infection in transplants, but dengue fever reported in renal transplants sheds some light on them. High-dose steroids increase the risk of thrombocytopenia, whereas tacrolimus has been reported to prolong the duration of symptoms. Otherwise, dengue fever is a relatively mild illness in patients who have undergone renal transplantation, and renal allograft survival has been reported to be 86% following dengue fever.Dengue is a rarely reported infection in patients who have undergone transplantation. A high degree of suspicion is required for diagnosis. Dengue NS1 antigen detection is a useful addition to the already existing methods of diagnosis. Steroids and tacrolimus have effects on the morbidity of the disease. Graft outcomes following the infection has been excellent in all reported cases.
- Knowledge, perceptions, and practices with respect to the prevention of dengue in a mid-Pacific coastal village of Costa Rica.
Egedus VL, Ortega JM, Obando AA Knowledge, perceptions, and practices with respect to the prevention of dengue in a mid-Pacific coastal village of Costa Rica. [Journal Article]Rev Biol Trop 2014 Sep; 62(3):859-67.Dengue fever is the fastest spreading, most prevalent and deadly arthropod-borne viral disease worldwide, present in over 125 countries. In 2013, Costa Rica is experiencing the highest number of Dengue infections since the virus's reintroduction to the country in 1993. This study evaluated the Dengue-related knowledge of 320 community members, and polled opinions on how to better educate and mobilize the community on Dengue prevention in Quebrada Ganado, Costa Rica during March-May, 2013. In addition, property inspections were used to find relationships between knowledge or opinions and presence ofAedes breeding sites. Results showed that while citizens knew the virus is transmitted by mosquitoes that reproduce near water, they lacked knowledge on Aedes habits and confused it with other mosquitoes. Eighty-one percent of respondents assumed some responsibility for dengue prevention. Suggestions for improved education included consistent and continual information on the risks and dangers dengue poses to an individual. Characteristics relating to households with more positive breeding sites were: lower education level, higher prevalence of dengue infections in the household, lesser knowledge of dengue symptoms, a lower rating on the dangers of dengue and a lower rating on the importance of preventative actions. While a range of prevention methods are implemented, active community involvement is highly important for successful Dengue prevention. Continual evaluation is necessary to make more immediate, long-term behavioral societal changes, and to maximize the economic resources spent on Dengue prevention.
- Approaches to Refining Estimates of Global Burden and Economics of Dengue.
Shepard DS, Undurraga EA, Betancourt-Cravioto M, et al. Approaches to Refining Estimates of Global Burden and Economics of Dengue. [JOURNAL ARTICLE]PLoS Negl Trop Dis 2014 Nov; 8(11):e3306.Dengue presents a formidable and growing global economic and disease burden, with around half the world's population estimated to be at risk of infection. There is wide variation and substantial uncertainty in current estimates of dengue disease burden and, consequently, on economic burden estimates. Dengue disease varies across time, geography and persons affected. Variations in the transmission of four different viruses and interactions among vector density and host's immune status, age, pre-existing medical conditions, all contribute to the disease's complexity. This systematic review aims to identify and examine estimates of dengue disease burden and costs, discuss major sources of uncertainty, and suggest next steps to improve estimates. Economic analysis of dengue is mainly concerned with costs of illness, particularly in estimating total episodes of symptomatic dengue. However, national dengue disease reporting systems show a great diversity in design and implementation, hindering accurate global estimates of dengue episodes and country comparisons. A combination of immediate, short-, and long-term strategies could substantially improve estimates of disease and, consequently, of economic burden of dengue. Suggestions for immediate implementation include refining analysis of currently available data to adjust reported episodes and expanding data collection in empirical studies, such as documenting the number of ambulatory visits before and after hospitalization and including breakdowns by age. Short-term recommendations include merging multiple data sources, such as cohort and surveillance data to evaluate the accuracy of reporting rates (by health sector, treatment, severity, etc.), and using covariates to extrapolate dengue incidence to locations with no or limited reporting. Long-term efforts aim at strengthening capacity to document dengue transmission using serological methods to systematically analyze and relate to epidemiologic data. As promising tools for diagnosis, vaccination, vector control, and treatment are being developed, these recommended steps should improve objective, systematic measures of dengue burden to strengthen health policy decisions.
- Evaluation of Multiple Antigenic Peptides Based on the Chikungunya E2 Protein for Improved Serological Diagnosis of Infection.
Bhatnagar S, Kumar P, Mohan T, et al. Evaluation of Multiple Antigenic Peptides Based on the Chikungunya E2 Protein for Improved Serological Diagnosis of Infection. [JOURNAL ARTICLE]Viral Immunol 2014 Nov 20.Abstract In recent years, Chikungunya virus (CHIKV) reemerged and numerous outbreaks were reported all over the world. After screening CHIKV-positive sera, we had already reported many dominant epitopes within the envelope E2 protein of CHIKV. In the present study, we aimed at developing a highly sensitive immunodiagnostic assay for CHIKV based on a multiple antigenic peptide (MAP) approach using selective epitopes of the E2 protein. MAPs in four different E2 peptide combinations were screened with CHIKV-positive sera. The MAPs reacted with all CHIKV-positive sera and no reactivity was seen with healthy or dengue-positive sera. Our results indicate that MAP 1 seems to be an alternate antigen to full-length protein E2 for immunodiagnosis of CHIKV infections with high sensitivity and specificity.
- Understanding Dengue Virus Capsid Protein Disordered N-Terminus and pep14-23-Based Inhibition.
Faustino AF, Guerra GM, Huber RG, et al. Understanding Dengue Virus Capsid Protein Disordered N-Terminus and pep14-23-Based Inhibition. [JOURNAL ARTICLE]ACS Chem Biol 2014 Nov 20.Dengue virus (DENV) infection affects millions of people and is becoming a major global disease for which there is no specific available treatment. pep14-23 is a recently designed peptide, based on a conserved segment of DENV capsid (C) protein. It inhibits the interaction of DENV C with host intracellular lipid droplets (LDs), which is crucial for viral replication. Combining bioinformatics and biophysics, here, we analyzed pep14-23 structure and ability to bind different phospholipids, relating that information with the full-length DENV C. We show that pep14-23 acquires α-helical conformation upon binding to negatively charged phospholipid membranes, displaying an asymmetric charge distribution structural arrangement. Structure prediction for the N-terminal segment reveals four viable homodimer orientations that alternatively shield or expose the DENV C hydrophobic pocket. Taken together, these findings suggest a new biological role for the disordered N-terminal region, which may function as an autoinhibitory domain mediating DENV C interaction with its biological targets. The results fit with our current understanding of DENV C and pep14-23 structure and function, paving the way for similar approaches to understanding disordered proteins and improved peptidomimetics drug development strategies against DENV and similar Flavivirus infections.
- Antibody-Dependent Enhancement Infection Facilitates Dengue Virus-Regulated Signaling of IL-10 Production in Monocytes.
Tsai TT, Chuang YJ, Lin YS, et al. Antibody-Dependent Enhancement Infection Facilitates Dengue Virus-Regulated Signaling of IL-10 Production in Monocytes. [JOURNAL ARTICLE]PLoS Negl Trop Dis 2014 Nov; 8(11):e3320.Interleukin (IL)-10 levels are increased in dengue virus (DENV)-infected patients with severe disorders. A hypothetical intrinsic pathway has been proposed for the IL-10 response during antibody-dependent enhancement (ADE) of DENV infection; however, the mechanisms of IL-10 regulation remain unclear.We found that DENV infection and/or attachment was sufficient to induce increased expression of IL-10 and its downstream regulator suppressor of cytokine signaling 3 in human monocytic THP-1 cells and human peripheral blood monocytes. IL-10 production was controlled by activation of cyclic adenosine monophosphate response element-binding (CREB), primarily through protein kinase A (PKA)- and phosphoinositide 3-kinase (PI3K)/PKB-regulated pathways, with PKA activation acting upstream of PI3K/PKB. DENV infection also caused glycogen synthase kinase (GSK)-3β inactivation in a PKA/PI3K/PKB-regulated manner, and inhibition of GSK-3β significantly increased DENV-induced IL-10 production following CREB activation. Pharmacological inhibition of spleen tyrosine kinase (Syk) activity significantly decreased DENV-induced IL-10 production, whereas silencing Syk-associated C-type lectin domain family 5 member A caused a partial inhibition. ADE of DENV infection greatly increased IL-10 expression by enhancing Syk-regulated PI3K/PKB/GSK-3β/CREB signaling. We also found that viral load, but not serotype, affected the IL-10 response. Finally, modulation of IL-10 expression could affect DENV replication.These results demonstrate that, in monocytes, IL-10 production is regulated by ADE through both an extrinsic and an intrinsic pathway, all involving a Syk-regulated PI3K/PKB/GSK-3β/CREB pathway, and both of which impact viral replication.
- Development, Characterization and Application of Monoclonal Antibodies against Brazilian Dengue Virus Isolates.
Zanluca C, Mazzarotto GA, Bordignon J, et al. Development, Characterization and Application of Monoclonal Antibodies against Brazilian Dengue Virus Isolates. [JOURNAL ARTICLE]PLoS One 2014; 9(11):e110620.Dengue is the most prevalent human arboviral disease. The morbidity related to dengue infection supports the need for an early, quick and effective diagnostic test. Brazil is a hotspot for dengue, but no serological diagnostic test has been produced using Brazilian dengue virus isolates. This study aims to improve the development of immunodiagnostic methods for dengue virus (DENV) detection through the production and characterization of 22 monoclonal antibodies (mAbs) against Brazilian isolates of DENV-1, -2 and -3. The mAbs include IgG2bκ, IgG2aκ and IgG1κ isotypes, and most were raised against the envelope or the pre-membrane proteins of DENV. When the antibodies were tested against the four DENV serotypes, different reactivity patterns were identified: group-specific, subcomplex specific (DENV-1, -3 and -4 and DENV-2 and -3) and dengue serotype-specific (DENV-2 or -3). Additionally, some mAbs cross-reacted with yellow fever virus (YFV), West Nile virus (WNV) and Saint Louis encephalitis virus (SLEV). None of the mAbs recognized the alphavirus Venezuelan equine encephalitis virus (VEEV). Furthermore, mAbs D3 424/8G, D1 606/A12/B9 and D1 695/12C/2H were used to develop a capture enzyme-linked immunosorbent assay (ELISA) for anti-dengue IgM detection in sera from patients with acute dengue. To our knowledge, these are the first monoclonal antibodies raised against Brazilian DENV isolates, and they may be of special interest in the development of diagnostic assays, as well as for basic research.
- Evaluation of Dengue NS1 Antigen Rapid Tests and ELISA Kits Using Clinical Samples.
Pal S, Dauner AL, Mitra I, et al. Evaluation of Dengue NS1 Antigen Rapid Tests and ELISA Kits Using Clinical Samples. [JOURNAL ARTICLE]PLoS One 2014; 9(11):e113411.Early diagnosis of dengue virus (DENV) infection can improve clinical outcomes by ensuring close follow-up, initiating appropriate supportive therapies and raising awareness to the potential of hemorrhage or shock. Non-structural glycoprotein-1 (NS1) has proven to be a useful biomarker for early diagnosis of dengue. A number of rapid diagnostic tests (RDTs) and enzyme-linked immunosorbent assays (ELISAs) targeting NS1 antigen (Ag) are now commercially available. Here we evaluated these tests using a well-characterized panel of clinical samples to determine their effectiveness for early diagnosis.Retrospective samples from South America were used to evaluate the following tests: (i) "Dengue NS1 Ag STRIP" and (ii) "Platelia Dengue NS1 Ag ELISA" (Bio-Rad, France), (iii) "Dengue NS1 Detect Rapid Test (1st Generation)" and (iv) "DENV Detect NS1 ELISA" (InBios International, United States), (v) "Panbio Dengue Early Rapid (1st generation)" (vi) "Panbio Dengue Early ELISA (2nd generation)" and (vii) "SD Bioline Dengue NS1 Ag Rapid Test" (Alere, United States). Overall, the sensitivity of the RDTs ranged from 71.9%-79.1% while the sensitivity of the ELISAs varied between 85.6-95.9%, using virus isolation as the reference method. Most tests had lower sensitivity for DENV-4 relative to the other three serotypes, were less sensitive in detecting secondary infections, and appeared to be most sensitive on Day 3-4 post symptom onset. The specificity of all evaluated tests ranged from 95%-100%.ELISAs had greater overall sensitivity than RDTs. In conjunction with other parameters, the performance data can help determine which dengue diagnostics should be used during the first few days of illness, when the patients are most likely to present to a clinic seeking care.
- Assessing Positivity and Circulating Levels of NS1 in Samples from a 2012 Dengue Outbreak in Rio de Janeiro, Brazil.
Allonso D, Meneses MD, Fernandes CA, et al. Assessing Positivity and Circulating Levels of NS1 in Samples from a 2012 Dengue Outbreak in Rio de Janeiro, Brazil. [JOURNAL ARTICLE]PLoS One 2014; 9(11):e113634.Dengue virus (DENV) represents a major threat to public health worldwide. Early DENV diagnosis should not only detect the infection but also identify patients with a higher likelihood to develop severe cases. Previous studies have suggested the potential for NS1 to serve as a viral marker for dengue severity. However, further studies using different sera panels are required to confirm this hypothesis. In this context, we developed a lab-based ELISA to detect and quantitate NS1 protein from the four DENV serotypes and from primary and secondary cases. This approach was used to calculate the circulating NS1 concentration in positive samples. We also tested the NS1 positivity of DENV-positive samples according to the Platelia Dengue NS1 Ag assay. A total of 128 samples were positive for DENV infection and were classified according to the WHO guidelines. The overall NS1 positivity was 68% according to the Platelia assay, whereas all samples were NS1-positive when analyzed with our lab-based ELISA. Fifty-four samples were positive by PCR, revealing a co-circulation of DENV1 and DENV4, and the NS1 positivity for DENV4 samples was lower than that for DENV1. The circulating NS1 concentration ranged from 7 to 284 ng/mL. Our results support previous data indicating the low efficiency of the Platelia assay to detect DENV4 infection. Moreover, this work is the first to analyze NS1 antigenemia using retrospective samples from a Brazilian outbreak.