Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “DENGUE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 667 records · Page 37Linked to original sources

Laboratory diagnosis of primary and secondary dengue infection.

BACKGROUND: Dengue fever is routinely detected in many laboratories using commercial tests for the specific detection of dengue IgM antibodies. OBJECTIVES: We have studied the sensitivity of IgM antibody detection in paired serum samples of 43 patients with either with primary dengue (PD) or secondary dengue (SD). STUDY DESIGN: Two consecutive samples were drawn from 23 Vietnamese and 20 German patients. All patients were selected for a positive PCR and for the fact that consecutive serum samples were available. The diagnosis of PD was based on seroconversion to dengue antigen and in SD on the detection of virus RNA in the presence of anti-dengue IgG antibodies. RESULTS: In samples of patients with PD fever taken during days 1-3 of the disease no IgM antibody could be detected. During days 4-7 and after day 7, IgM antibody was detected in 55% and 94%, respectively. In patients with SD fever, even less positive IgM samples were found in samples taken during days 4-7 (47%) and after day 7 (78%). IgG titers were significantly higher in SD compared to PD patients, although high (>1280) titers were also found in some PD patients. CONCLUSION: In numerous acute dengue fever patients an early diagnosis will be obtained only by combining IgM antibody detection with detection of virus or virus RNA using RT-PCR.

Antibodies, Viral↗

Simultaneous infection with dengue 2 and 3 viruses in a Chinese patient return from Sri Lanka.

Dengue is an acute viral disease transmitted by the Aedes aegypti and Aedes albopictus mosquito, which are present in most tropical urban areas of the world. There are four antigenically distinct serotypes, designated dengue-1 (DEN-1), dengue-2 (DEN-2), dengue-3 (DEN-3) and dengue-4 (DEN-4). Dengue outbreaks have occurred in several regions in Asia, involving four serotypes of dengue 1, 2, 3 and 4. In review of the few cases of dual infection documented in the literature, we report here a case of simultaneous infection with DEN-2 and DEN-3 in a Chinese patient return from Sri Lanka. The dual infection was identified by type-specific indirect immunofluorescence assay and confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) and sequence determination. This is the first documented case of simultaneous infection with serotype of DEN-2 and DEN-3 in China.

Adult↗

Antibodies from patients with dengue viral infection mediate cellular cytotoxicity.

Acute and late convalescent sera (collected at day 5 of disease onset and 1 year later) from dengue fever (DF) and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) laboratory confirmed cases, were tested for antibody-dependent cell-mediated cytotoxicity (ADCC) activity using dengue 1 (DENV-1) or dengue 2 (DENV-2) infected cells as target. All patients experienced their first dengue virus (DENV) infection 20 years before. ADCC activity was detected in acute sera from DHF/DSS but not in sera from DF patients. However, 1 year after illness, ADCC activity was observed in all cases. This preliminary report represents one of the few studies of ADCC in dengue patients and suggests that ADCC could be implicated in dengue pathogenesis.

Antibodies, Viral↗

Dengue infection during pregnancy and transplacental antibody transfer in Thai mothers.

OBJECTIVES: The objectives of this study were to estimate dengue seroprevalence in a population of Thai pregnant women, living in a highly endemic area and placental transfer of dengue antibodies. METHODS: A cross-sectional seroprevalence study of 245 pregnant women at delivery. RESULTS: Dengue HAI antibodies were positive in 94.7%. Maternal age was the only risk factor associated with dengue infection as older mothers (>20 years) were significantly more likely to be seropositive than younger women (p<0.0001). Cord antibody titres varied with maternal age and antibody titre, were significantly higher in babies born to younger mothers (<20 years) (p=0.01), and were significantly correlated with maternal titre. Low birthweight babies had lower transfer ratios for DEN-2 antibody (1.06) compared to heavier babies (1.36, p=0.05). No mother or neonate had dengue IgM detected. Two women were classified as recently, but not currently infected with dengue virus and we consider it likely these were first trimester infections. As no infant became infected the fetal infection was 0%. CONCLUSIONS: Younger mothers were more likely to have been recently infected, resulting in higher antibody titres. Maternal dengue antibody transfer was proportional to maternal antibody concentration.

Adolescent↗

Dengue typing assay based on real-time PCR using SYBR Green I.

Typing of dengue virus is crucial for the epidemiology and pathogenesis of dengue virus infection. Hence, highly sensitive and accurate diagnostic tools are essential. The purpose of this study was to identify all four types of dengue virus based on the 3'-untranslated region of the virus by melting curve analysis and real-time PCR using SYBR Green I. The types obtained by this method were compared with the results of direct sequencing of 39 serum or plasma samples of patients with clinical dengue infection that included a positive tourniquet test, thrombocytopenia and positive dengue IgM antibody. The accuracy of typing by melting curve analysis was 97.4%. In conclusion, real-time PCR and melting curve analysis using one single-primer pair were shown to be highly efficient for clear detection and typing of dengue virus in clinical specimens. This method therefore represents a simple, sensitive, specific, rapid and economic method, which will be essential for epidemiological studies of dengue virus infection.

Benzothiazoles↗

Induction of protective antibodies against dengue virus by tetravalent DNA immunization of mice with domain III of the envelope protein.

Dengue fever is a growing public health concern around the world and despite vaccine development efforts, there are currently no effective dengue vaccines. In the present study we report the induction of protective antibodies against dengue virus by DNA immunization with domain III (DIII) region of the envelope protein (E) in a mouse model. The DIII region of all four dengue virus serotypes were cloned separately into pcDNA 3 plasmid. Protein expression was tested in COS-7 cells. Each plasmid, or a tetravalent combination, were used to immunize BALB/c mice by intramuscular route. Presence of specific antibodies was evaluated by ELISA, and neutralizing antibodies were tested using a cytopathogenic effect (CPE) inhibition assay in BHK-21 cells, as well as in newborn mice challenged intracranially with dengue 2 virus. Mice immunized with individual DIII constructs or the tetravalent formulation developed antibodies against each corresponding dengue serotype. Antibody titers by ELISA were similar for all serotypes and no significant differences were observed when boosters were administered, although antibody responses were dose-dependent. CPE inhibition assays using Den-2 virus showed neutralization titers of 1:10 in mice immunized with individual DIII plasmid or those immunized with the tetravalent formulations. 43% of newborn mice challenged with Den-2 in combination with sera from mice immunized with Den-2 DIII plasmid were protected, whereas sera from mice immunized with the tetravalent formulation conferred 87% protection. Our results suggest that DIII can be used as a tetravalent DNA formulation to induce neutralizing and protective antibodies against dengue virus.

Animals↗

Dengue: emergence as a global public health problem and prospects for control.

Dengue causes more illness and death than any other arboviral infection: there are at least 20 million infections in the world each year and several hundred thousand cases of a severe, life-threatening syndrome known as dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS). In recent years, the geographical range of dengue has extended and DHF/DSS is occurring in new areas and with increased incidence. The reasons for the resurgence are complex, but parallel demographic changes and reduced efforts towards disease control. Control of dengue currently depends on controlling its mosquito vector. However, development of a vaccine offers greater hope in the long-term. The dengue group of flaviviruses is unique in that it comprises 4 distinct serotypes which have the potential to cause sequential infections with increased severity. It is reasoned, therefore, that any vaccine should induce solid immunity to all 4 serotypes. Knowledge regarding dengue immunity and pathogenesis is rapidly advancing and it is reasonable to believe that this information can be used to devise a safe and efficacious vaccine for dengue, but it seems unlikely that this will become available in the near future.

Dengue↗

A dengue virus serotype-1 DNA vaccine induces virus neutralizing antibodies and provides protection from viral challenge in Aotus monkeys.

A DNA vaccine that expresses the premembrane/membrane (prM) and envelope (E) genes of dengue virus serotype-1 was tested for immunogenicity and protection against dengue-1 virus challenge in Aotus nancymae monkeys. The vaccine, in 1 mg doses, was administered intradermally (i.d.) to three monkeys and intramuscularly (i.m.) to three others. For controls, a 1 mg dose of vector DNA was administered i.d. to two monkeys and i.m. to one. All animals were primed and then boosted at one and five months post priming. Sera were collected monthly and analyzed for dengue-1 antibodies by enzyme linked immunosorbent assay (ELISA) and plaque reduction neutralization test (PRNT). Dengue-1 antibodies were detectable in the sera from i.d. and i.m. vaccine inoculated animals one month after the first boost and peaked one month after the second boost. The antibody levels from sera of animals that received the vaccine via the i.d. route were twice those from sera of animals that received the vaccine via the i.m. route. Six months after the second boost all inoculated and two naive monkeys were challenged with 1.25x10(4) plaque forming units (PFU) of dengue-1 virus. Two vaccine immunized animals were protected from viremia while the others showed a reduction in viremia. The mean days of viremia were 1 and 1.3 for the animals that were immunized with the vaccine via the i.d. or i.m. route, respectively vs 4 and 2 mean days of viremia in the animals inoculated with control DNA. Naive animals were viremic for an average of 4 days. All of the three control monkeys that received control DNA inoculum by either the i.d. or i.m. route had an intermittent viremia pattern with one or more negative days interspersed between the positive days. This pattern was not observed in any of the vaccine recipients or the naïve control monkeys. These results demonstrate that DNA immunization is a promising approach for the development of dengue vaccines and that A. nancymae monkeys are suitable for dengue vaccine trials.

Animals↗

Mechanisms of dengue virus-induced bone marrow suppression.

Infection with many flaviviruses is associated with transient suppression of haematopoiesis. Of the flaviviruses of man, none are more accessible to clinical and laboratory study than dengue. Consequently, the clinical syndrome of dengue-associated bone marrow suppression has been well documented. A review of experimental dengue infections of volunteers and histopathological studies of bone marrow from patients with severe dengue virus infection suggests that marrow suppression evolves rapidly through several phases: (1) onset of marrow suppression within 3-4 days of infection; (2) onset of host inflammatory responses in the marrow and of fever shortly thereafter; (3) occurrence of a neutrophil nadir on the fourth to fifth day after onset of fever; (4) almost simultaneously, immune activation sufficient to neutralize viraemia and accelerate elimination of infected cells; (5) remission of symptoms; and (6) resolution of cytopenias. Clinical observations and experimental data bear on possible mechanisms of dengue virus-mediated marrow suppression. Work from the authors' laboratory in which long-term bone marrow cultures were used to investigate interactions between dengue virus and bone marrow cells (stromal elements and haematopoietic progenitors) is also reviewed. Long-term marrow culture (LTMC) was a useful experimental system. In vitro, early blast cells as well as the more differentiated haematopoietic elements were abortively infected, killed and eliminated by phagocytosis by specialized marrow macrophages called dendritic cells. Moreover, the ARC from stroma rather than haematopoietic precursors were productively infected. When ARC were infected, stroma failed to support haematopoiesis. Cytokine production by virus-infected stromal cells was altered. A hypothesis is proposed to account for dengue virus-induced marrow suppression. Down-regulation of haematopoiesis is probably a protective mechanism of the microenvironment that limits injury to the marrow stem/progenitor cell compartment during the subsequent process of elimination of infected cells.

Bone Marrow↗

Dengue: the risk to developed and developing countries.

Dengue viruses are members of the Flaviviridae, transmitted principally in a cycle involving humans and mosquito vectors. In the last 20 years the incidence of dengue fever epidemics has increased and hyperendemic transmission has been established over a geographically expanding area. A severe form, dengue hemorrhagic fever (DHF), is an immunopathologic disease occurring in persons who experience sequential dengue infections. The risk of sequential infections, and consequently the incidence of DHF, has risen dramatically, first in Asia and now in the Americas. At the root of the emergence of dengue as a major health problem are changes in human demography and behavior, leading to unchecked populations of and increased exposure to the principal domestic mosquito vector, Aedes aegypti. Virus-specified factors also influence the epidemiology of dengue. Speculations on future events in the epidemiology, evolution, and biological expression of dengue are presented.

Aedes↗

Immune complex: does it have a role in pathogenesis of renal failure in dengue infection?

Dengue infection is a major public health problem. When acute renal failure complicates dengue infection, it is usually associated with severe disease as in dengue hemorrhagic fever or dengue shock syndrome. The role of immune complex in development of renal failure in dengue infection is still unclear. Here, the author used a computational medicine technology to study the property of the dengue virus-immunoglobulin complex. According to this study, the diameter of derived complex is much smaller, compared with the diameter of glomerulus. Entrapment of the immune complex is believed to occur when a previous glomerular lesion causes narrowing of the glomerulus's diameter. Therefore, the immune complex should not have a significant role in pathogenesis of renal failure in dengue infection.

Acute Kidney Injury↗

Status of antioxidants and other biochemical abnormalities in children with dengue fever.

During an outbreak of dengue fever in 1996, 66 children between 45 days and 12 years of age with dengue fever and 25 healthy controls were studied for antioxidants and other biochemical abnormalities. As per World Health Organization (WHO) criteria, 14 children were classified as having classical dengue (DEN), 42 with dengue haemorrhagic fever (DHF), and 10 (including three who died) as having dengue shock syndrome (DSS). Superoxide dismutase (SOD), glutathione peroxidase (GPX), and albumin (ALB), the three main antioxidants studied, were found to be abnormal in 96, 94, and 40 per cent of the cases respectively. The levels for aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine phosphokinase (CPK), total protein (TP), total cholesterol (CHO), and triglycerides (TGL) were abnormal in 79, 50, 30, 93, and 67 per cent of the cases respectively. Among the different groups of dengue the abnormalities were more marked in children with DSS than in those with DEN and DHF, especially with respect to ALB, TP, TGL, AST, ALT, and CPK (p < 0.005). This preliminary report of dengue confirms the assumption of free radical generation and alteration in antioxidant status during acute illness. However, to understand their complex interaction in disease progression and therapeutic utility, further studies are required.

Antioxidants↗

High levels of sTNFR p75 and TNF alpha in dengue-infected patients.

Soluble forms of the two molecular species of the cell surface TNF receptors (sTNFR p55 and sTNFR p75) can reduce the activity of TNF alpha but they may also enhance its function by stabilizing the active TNF alpha oligomer. Considering the pathophysiological importance of sTNFR p75 for the regulation of the bioavailability of TNF alpha in the body, we determined the serum levels of sTNFR p75 and TNF alpha in 45 children and 28 adults with laboratory-confirmed dengue infection by using immunoassays. The serum samples were obtained from day 1 to day 15 after the onset of the disease during the 1989-1990 outbreak of dengue-3 in Tahiti, French Polynesia. The patients were clinically classified as having dengue hemorrhagic fever (DHF) and graded according to the criteria of the World Health Organization (WHO) into four grades from less severe (grade I) to severe (grade IV). The sera of both children and adult patients of all severity grades contained higher levels of sTNFR p75 than the sera of control subjects. Although high levels of TNF alpha were also detected in children and adults among grade I, II, III and IV patients, we found no correlation between sTNFR p75 and TNF alpha. We observed in adults a moderate elevation of sTNFR p75 and TNF alpha in sera compared with that observed in children. The raised levels of immunoreactive sTNFR p75 and TNF alpha in all clinical groups of dengue-infected patients strongly indicate activation of the TNF alpha system during dengue infection. The balance between sTNFR p75 and TNF alpha may be altered in dengue infection. Further investigations are needed to understand the role of sTNFR p75 and TNF alpha in the pathogenesis of DHF and to improve the management of dengue infection.

Adult↗

Seroprevalence of dengue antibodies, annual incidence and risk factors among children in southern Vietnam.

Dengue is highly endemic in southern Vietnam and all four serotypes of dengue virus have already been identified. To determine the age-specific prevalence of dengue and associated risk factors, we conducted a serological study at two primary schools and assessed risk factors by analysing children's questionnaires and household surveys. Sera were collected from 961 primary schoolchildren in Binh Thuan Province and tested for the presence of dengue virus serum antibodies using an indirect immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA). The antibody prevalence of the total population was 65.7% (n=631) which increased from 53.0 to 88.2% with age. The annual incidence of a first dengue infection, estimated by binary regression of the seroprevalence by age, was 11.7%. Interestingly, the prevalence of dengue IgG antibodies was significantly higher in children who confirmed using a pit latrine (RR 1.467, 95% CI: 1.245-1.730) and whose domestic environment contained discarded cans (RR 1.238, 95% CI: 1.042-1.470) and pigs (RR 1.228, 95% CI: 1.002-1.504). The epidemiology of dengue in southern Vietnam is stable with a constantly high annual incidence of first infections. Transmission occurs mainly peri-domestically, which has important public health implications.

Adolescent↗

Diagnosis of dengue virus infection by the visual and simple AuBioDOT immunoglobulin M capture system.

The Dengue IgM Capture ELISA (MAC-ELISA) is the immunoenzymatic system recommended by the Pan American Health Organization and the World Health Organization for the serological diagnosis of dengue virus infection due to its high sensitivity, ease of performance, and use of a single acute-phase serum sample. However, tests with this enzyme-linked immunosorbent assay (ELISA) system are time-consuming and require equipment for washing, incubation, and reading of the results. AuBioDOT is a multistep visual diagnostic immunoassay that uses technology based on the immunoglobulin M (IgM) capture ELISA principle. This system uses white polyethylene opaque plates as the solid phase, colloidal gold as the marker, and silver ion amplification. It does not require special equipment, it is totally manually operated, and it can be performed in less than 1 h. The sensitivity and specificity of AuBioDOT for the detection of anti-dengue virus IgM antibodies were studied with a panel of 336 serum samples (150 serum samples from patients with suspected or serologically confirmed dengue virus infection, 186 serum samples from healthy blood donors and patients without dengue virus infection). The results were compared with those obtained by the MAC-ELISA. A sensitivity of 97.7% and a specificity of 97.1% were obtained. The concordance of the two tests was 97.3%, with a kappa index of 0.94. The application of AuBioDOT for the detection of anti-dengue virus IgM antibodies is recommended as an alternative method for the diagnosis of dengue virus infection, both for clinical diagnosis and for seroepidemiological surveillance. The system is useful under field conditions and in laboratories and requires little equipment.

Antibodies, Viral↗

Serotype-cross-reactive immunoglobulin M responses in dengue virus infections determined by enzyme-linked immunosorbent assay.

We developed immunoglobulin M (IgM) antibody capture enzyme-linked immunosorbent assays (ELISAs) with four monovalent dengue virus antigens. We attempted to determine whether IgM responses in dengue virus infections are serotype specific or serotype cross-reactive. Serum samples from 14 confirmed dengue cases were examined. In these 14 cases, which consisted of 12 Japanese and 2 non-Japanese patients, infecting dengue virus serotypes were defined by reverse transcription-PCR. Thirteen of the 14 cases were IgM positive in ELISA. IgM responses were serotype cross-reactive in these 13 cases but were highest against infecting dengue virus serotype in 9 of the 13 cases. These results indicate that IgM responses are generally dengue serotype cross-reactive but that IgM levels are highest against the infecting serotype in most dengue cases.

Aedes↗

Use of capillary blood samples as a new approach for diagnosis of Dengue virus infection.

We evaluated the use of capillary blood samples stored on filter papers for diagnosis of dengue virus infection. Venous and capillary blood samples were collected from 130 patients suspected of having dengue fever. We compared the performances of standard reference methods using capillary blood samples absorbed onto filter papers versus venous blood samples. The resulting sensitivity, specificity, and positive predictive value of tests performed on filter paper compared to those performed on venous blood samples were 81.6% (62/76; 95% confidence interval [CI], 74.9% to 88.3%), 90.7% (49/54; 95% CI, 85.7% to 95.7%), and 92.5% (62/67; 95% CI, 86.2% to 98.8%), respectively. During the acute phase of dengue virus infection (day 1 to day 4), the tests performed on capillary blood samples had a sensitivity of 88.5% (95% CI, 82.0% to 95.0%) and a specificity of 93.8% (95% CI, 88.9% to 98.7%). During the convalescent phase of infection, this method allowed the viral serotype to be determined for 4 of 15 (27%) dengue virus-infected patients for whom virological diagnosis using venous samples was negative. Capillary blood samples could therefore be a good alternative for the diagnosis of dengue virus infection in tropical areas. Indeed, these samples are convenient for storage and transport without the need for a cold chain and simplify the collection of samples from children. Moreover, our results suggest that viral particles persist longer in capillary blood than in peripheral blood. Analysis of the viability of viral particles under these conditions may give new insights into the physiopathology of dengue virus infection and the transmission of dengue virus during outbreaks.

Aedes↗

Monkeys immunized with intertypic chimeric dengue viruses are protected against wild-type virus challenge.

Dengue epidemics caused by the four dengue virus serotypes continue to pose a major public health problem in most tropical and subtropical regions. A safe and effective vaccine against dengue is still not available. The current strategy for dengue immunization favors the use of a vaccine containing each of the four serotypes. We previously employed full-length dengue type 4 virus (DEN4) cDNA to construct a viable intertypic dengue virus of type 1 or type 2 antigenic specificity that contained the genes for the capsid-premembrane-envelope (C-pre-M-E) structural proteins of DEN1 or pre-M and E structural proteins of DEN2 substituting for the corresponding DEN4 genes. Chimeras DEN1/DEN4 and DEN2/DEN4, which express the nonstructural proteins of DEN4 and the C-pre-M-E structural proteins of DEN1 or the pre-M-E structural proteins of DEN2, and therefore the antigenicity of type 1 or type 2, were used to immunize rhesus monkeys. Other monkeys were inoculated with parental DEN1, DEN2, or cDNA-derived DEN4. Three of four monkeys immunized with DEN1/DEN4 developed neutralizing antibodies against DEN1 and were protected against subsequent DEN1 challenge. All four monkeys immunized with DEN2/DEN4 developed antibodies against DEN2 and were protected against subsequent DEN2 challenge. DEN1- and DEN2-immunized monkeys were protected against homologous virus challenge, but DEN4-immunized animals became viremic on cross-challenge with DEN1 or DEN2. In a second experiment, eight monkeys were immunized with equal mixtures of DEN1/DEN4 and DEN2/DEN4. Each of these monkeys developed neutralizing antibodies against both DEN1 and DEN2 and were protected against subsequent challenge with DEN1 or DEN2. Chimeric dengue viruses similar to those described here could be used to express serotype-specific antigens in a live attenuated tetravalent human vaccine.

Animals↗