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PubMed2003

A novel reverse transcriptase-polymerase chain reaction based-liquid hybridisation (RT-PCR-LH) assay for early diagnosis of dengue infection.

BACKGROUND: Early definitive laboratory diagnosis of dengue is difficult with the tests in routine use at present. OBJECTIVE: To develop a reverse transcriptase-polymerase chain reaction based liquid hybridisation (RT-PCR-LH) technique for the rapid and early diagnosis of dengue. RESEARCH DESIGN: RT-PCR products of the NS3 gene of dengue virus prototypes and of a few positive sera for dengue virus by culture, were allowed to hybridise in liquid phase with a mixture of dengue specific radiolabelled oligonucleotides. The products were separated by PAGE and visualised by autoradiography. 78 suspected dengue sera were also tested by RT-PCR-LH method, and by IgM-ELISA and HAI tests, for comparison. RESULTS: Two DNA bands (approximately equal to 470 bp and approximately equal to 455 bp) specific to dengue virus, were observed. RT-PCR-LH assay takes only 24 h. Of the 78 suspected dengue acute sera tested, 45/78 were positive by RT-PCR-LH, 31/78 were positive by IgM-ELISA, and 14/78 had a HAI titre > or = 2560. Duration of fever was known in 72 cases, and infection was detected by RT-PCR-LH in 11/22 of cases with < 5 d fever and by IgM-ELISA in 1/22. In cases with 5 to 15 d fever RT-PCR-LH and IgM-ELISA/HAI titre > or = 2560 detected infection in 30/50 and 27/50 respectively. The 10 sera which were negative by RT-PCR-LH, but were positive by either IgM-ELISA or HAI titre > or = 2560 were all > 5 d fever cases. RT-PCR-LH together with IgM-ELISA were capable of detecting dengue infection in 56/78 of the suspected cases. CONCLUSION: RT-PCR-LH assay developed in this study appears to have an advantage over other diagnostic techniques for the early detection of dengue.

Cohort Studies↗
PubMed1988

A prospective study of dengue infections in Bangkok.

Dengue infections were prospectively studied among 4- to 16-year-old students at a Bangkok school. Blood samples were obtained from 1,757 students in June 1980, before the dengue season, and in January 1981, after the season, and tested for dengue antibodies by the hemagglutination inhibition method. Classrooms were monitored daily for school absences. Fifty percent of the children had antibodies to, and were presumably immune to, at least 1 dengue serotype by the age of 7 years. Most (90/103, 87%) students who became infected by dengue viruses during the study period were either asymptomatic or minimally symptomatic (absent only 1 day). Most (7/13, 53%) of the symptomatic dengue infections (absent with fever for greater than or equal to 2 days) were clinically recognized as cases of dengue hemorrhagic fever which required hospitalization. None of 47 primary dengue infections required hospitalization, whereas 7 of 56 secondary infections did (P = 0.012). Preexistent dengue immunity, as detected by conventional serologic techniques, was a significant (odds ratio greater than or equal to 6.5) risk factor for development of dengue hemorrhagic fever.

Adolescent↗
PubMed2003

Phase I trial of 16 formulations of a tetravalent live-attenuated dengue vaccine.

Laboratory-attenuated strains of each of the four dengue serotypes previously tested as monovalent vaccines in volunteers were combined and tested for immunogenicity, safety, and reactogenicity in 16 dosage combinations. Tetravalent vaccines made using combinations of high (10(5-6) plaque-forming units [PFU]/dose) or low (10(3.5-4.5) PFU/dose) dosage formulations of each of the four viruses were inoculated in 64 flavivirus non-immune adult volunteers to determine which, if any, formulation raised neutralizing antibodies in at least 75% of volunteers to at least three of four dengue serotypes following one or two inoculations. Such formulations, if safe and sufficiently non-reactogenic, would be considered for an expanded Phase II trial in the future. Formulations 1-15 were each inoculated into three or four volunteers (total = 54) on days 0 and 28. Formulation 16 was tested in 10 volunteers, five volunteers inoculated on days 0 and 30, one volunteer on days 0 and 120, and four volunteers on days 0, 30, and 120. Blood was drawn for serologic assays immediately before and one month after each vaccination, and for viremia assay on day 10 after each vaccination. The 16 formulations were safe, but variably reactogenic after the first vaccination, and nearly non-reactogenic after the second and third vaccinations. Reactogenicity was positively correlated with immunogenicity. Similar proportions of volunteers seroconverted to dengue-1 (69%), dengue-2 (78%), and dengue-3 (69%), but significantly fewer volunteers seroconverted to dengue-4 (38%). The geometric mean 50% plaque reduction neutralization test titers in persons who seroconverted were significantly higher to dengue-1 (1:94) than to dengue-2 (1:15), dengue-3 (1:10), and dengue-4 (1:2). Seven formulations met the serologic criteria required for an expanded trial, and three of these were sufficiently attenuated clinically to justify further testing.

Adolescent↗
PubMed1992

The XXth century dengue pandemic: need for surveillance and research.

By the last decade of the XXth century Aedes aegypti and the 4 dengue viruses had spread to nearly all countries of the tropical world. Some 2 billion persons live in dengue-endemic areas with tens of millions infected annually. Dengue pandemics were also documented in the XVIIIth and XIXth centuries; they were contained by organized anti-Aedes aegypti campaigns and urban improvements. The XXth century dengue pandemic has brought with it the simultaneous circulation of multiple serotypes and in its aftermath, endemic dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS). Nearly 3 million children have been hospitalized with this syndrome in the past 3 decades, mainly in South-East Asia. Recent outbreaks of DHF/DSS in the Pacific Islands, China, India, Sri Lanka, Cuba and Venezuela are indicators of the high intensity and rapid spread of dengue transmission. The magnitude of the XXth century dengue pandemic requires urgent improvements in early warning surveillance by WHO Member States and the development of the capacity to study underlying mechanisms of the disease. A key research question is why does DHF/DSS not occur with all second dengue infections? Two answers have been suggested: (1) a human resistance gene. Data from the 1981 DHF/DSS epidemic in Cuba have demonstrated the existence in blacks of a resistance gene. The effect of such a gene in reducing disease susceptibility of American and African blacks requires more study. (2) The existence of dengue "biotypes". Some, but not all biotypes may cause DHF/DSS during a second dengue infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Aedes↗
PubMed1991

Antibody-dependent enhancement of dengue virus infection mediated by bispecific antibodies against cell surface molecules other than Fc gamma receptors.

It is known that antibodies to dengue viruses at subneutralizing concentrations enhance dengue virus infection of Fc gamma R+ cells. This phenomenon called antibody-dependent enhancement (ADE) occurs when virus-antibody complexes bind to the Fc gamma R via the Fc portion of the Ig. It has been hypothesized that ADE may be responsible for the pathogenesis of the severe manifestations of dengue virus infection including dengue hemorrhagic fever/dengue shock syndrome. To further analyze the mechanisms of ADE, we prepared bispecific antibodies by chemically cross-linking antidengue virus antibodies to antibodies specific for Fc gamma RI or Fc gamma RII and the non-Fc R molecules beta2 microglobulin, CD15 or CD33 and examined whether these bispecific antibodies could enhance infection. Bispecific antibodies targeting dengue virus to Fc gamma RI or Fc gamma RII enhanced dengue virus infection, consistent with previous reports using conventional antibodies. Furthermore, bispecific antibodies targeting dengue virus to beta2 microglobulin, CD15 or CD33 also enhanced dengue virus infection. Bispecific antibody mediated ADE was inhibited by pretreating the cells with the appropriate blocking mAb. These results indicate that cell surface molecules other than Fc gamma R can mediate ADE and suggest that the Fc gamma R does not provide a unique signal necessary for enhanced infection. We hypothesize that directing dengue virus to the cell surface by a bispecific antibody facilitates the interaction between dengue virus and its receptor, thereby increasing its infectivity.

Antibodies, Viral↗
PubMed2006

Incidence of dengue in a tertiary care centre--Kasturba Hospital, Manipal.

Dengue is the most important Arbovirus in the world in terms of occurrence and impact. It has been responsible for some devastating outbreaks and accounts for nearly 50-100 million cases of dengue fever and 2-5 lac cases of the dengue hemorrhagic fever worldwide. Dengue is caused by an arbovirus, which belongs to the Flaviviridae and is maintained in nature principally through biological transmission between susceptible vertebrate hosts by hematophagous arthropods. The incidence and global distribution of dengue has greatly increased in recent years and affects almost every country between the topics of Capricorn and Cancer. Although outbreaks of dengue fever has been occurring with regularity all over the country, and there have been 2 reported outbreaks in the neighboring district Mangalore in 1993 and 1996, there has been no reported outbreak in Manipal, which is what is responsible for the present study. In the study, out of the 100 clinically suspected cases of dengue, 44% tested positive for dengue IgM antibody, thus proving current dengue infection. Twenty six cases were from Shimoga district, which indicates increased dengue virus activity in this area and the possible endemicity in the region.

Antibodies, Viral↗
PubMed1996

[Prediction and prevention of dengue epidemics].

Prediction and prevention of dengue epidemics are based on informations gathered about the mosquito vector species, the dengue types transmitted, the vertebrate hosts and their environment. Although Aedes aegypti is the most important vector, other Aedes may also propagate the dengue viruses. The populations of vector mosquitoes are evaluated through several indices: Breteau and/or positive house index, number of indoor resting Aedes females, etc.... The four dengue types can replicate in vertebrate hosts beside humans and in other mosquito species than Ae. aegypti. The incidence of dengue on a population is largely variable according to the immunity status, the vector competence and the virus strains. Concomitant infections by two types of dengue virus or by an another pathogen (Alphavirus) have been observed. The environmental factors influencing the dengue ecosystem are mostly climatic (temperature, rainfall, wind) but also anthropic (transportation means, public buildings). Prevention of dengue epidemics must be based on public health education in schools, community participation, epidemiological surveillance linked with good vector control teams. Nevertheless intensive research on dengue and the actions undertaken for the last forty years, dengue remains the first cause of viral morbidity worldwide.

Aedes↗
PubMed1996

[The situation of dengue in the world].

The situation of dengue in the world can be summarized as follows: 2,5 billions persons at risk, 60 millions cases per year, and 30 000 deaths per year. The four dengue serotypes, DEN-1, DEN-2, DEN-3 and DEN-4 are nearly human-specific. Clinical symptoms of dengue vary from unapparent infection, mild febrile manifestations to hemorrhagic forms with or without shock syndrome. Dengue viruses are transmitted by Aedes mosquitoes, the most important vectors being Aedes aegypti and Aedes albopictus. The epidemiology of the disease can be divided into endemo-epidemic situations occurring in South-East Asia, and epidemic situations found in Pacific islands, Africa and Tropical America. Maintenance of dengue is supported by an increasing demography, uncontrolled urbanization and climatic conditions favorable to the vectors. Spread of dengue is primarily caused by modern transportation means, especially the aircraft. The geographical distribution of dengue is pantropical, except for Madagascar and some african regions. Because no vaccine and no specific treatment actually exist against dengue viruses, mosquito control is the only way to reduce the incidence of dengue around the world. However, the evolution of the dengue situation is not satisfactory.

Dengue↗
PubMed1997

Impact of dengue virus infection and its control.

Dengue virus infection has been counted among emerging and re-emerging diseases because of (1) the increasing number of patients, (2) the expansion of epidemic areas, and (3) the appearance of severe clinical manifestation of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS), which is often fatal if not properly treated. In the meantime, there are no effective dengue control measures: a dengue vaccine is still under development and vector control does not provide a long-lasting effect. In order to obtain direct evidence for the virulent virus theory concerning the pathogenesis of DHF/DSS, type 2 dengue virus strains isolated from patients with different clinical severities in the same epidemic area in northeast Thailand, during the same season, were comparatively sequenced. The result revealed a DF strain specific amino acid substitution from I to R in the PrM, and a DSS strain specific amino acid substitution from D to G in the NS1 gene regions, which could significantly alter the nature of these proteins. Moreover, DF strain specific nucleotide substitutions in the 3' noncoding region were predicted to alter its secondary structure. These amino acid and nucleotide substitutions in other strains isolated in different epidemic areas during other seasons, together with their biological significance, remain to be confirmed. In order to innovate dengue vector control, field tests were carried out in dengue epidemic areas in Vietnam to examine the efficacy of Olyset Net screen, which is a wide-mesh net made of polyethylene thread impregnated with permethrin. The results show that Olyset Net (1) reduced the number of principal dengue vector species, Aedes aegypti, (2) interrupted the silent transmission of dengue viruses and (3) was highly appreciated by the local people as a convenient and comfortable vector control method. This encouraging evaluation of the Olyset Net screen should be confirmed further by other tests under different settings.

Aedes↗
PubMed2004

Multi-analyte single-membrane biosensor for the serotype-specific detection of Dengue virus.

A multi-analyte biosensor based on nucleic acid hybridization and liposome signal amplification was developed for the rapid serotype-specific detection of Dengue virus. After RNA amplification, detection of Dengue virus specific serotypes can be accomplished using a single analysis within 25 min. The multi-analyte biosensor is based on single-analyte assays (see Baeumner et al (2002) Anal Chem 74:1442-1448) developed earlier in which four analyses were required for specific serotype identification of Dengue virus samples. The multi-analyte biosensor employs generic and serotype-specific DNA probes, which hybridize with Dengue RNA that is amplified by the isothermal nucleic acid sequence based amplification (NASBA) reaction. The generic probe (reporter probe) is coupled to dye-entrapping liposomes and can hybridize to all four Dengue serotypes, while the serotype-specific probes (capture probes) are immobilized through biotin-streptavidin interaction on the surface of a polyethersulfone membrane strip in separate locations. A mixture of amplified Dengue virus RNA sequences and liposomes is applied to the membrane and allowed to migrate up along the test strip. After the liposome-target sequence complexes hybridize to the specific probes immobilized in the capture zones of the membrane strip, the Dengue serotype present in the sample can be determined. The amount of liposomes immobilized in the various capture zones directly correlates to the amount of viral RNA in the sample and can be quantified by a portable reflectometer. The specific arrangement of the capture zones and the use of unlabeled oligonucleotides (cold probes) enabled us to dramatically reduce the cross-reactivity of Dengue virus serotypes. Therefore, a single biosensor can be used to detect the exact Dengue serotype present in the sample. In addition, the biosensor can simultaneously detect two serotypes and so it is useful for the identification of possible concurrent infections found in clinical samples. The various biosensor components have been optimized with respect to specificity and sensitivity, and the system has been ultimately tested using blind coded samples. The biosensor demonstrated 92% reliability in Dengue serotype determination. Following isothermal amplification of the target sequences, the biosensor had a detection limit of 50 RNA molecules for serotype 2, 500 RNA molecules for serotypes 3 and 4, and 50,000 molecules for serotype 1. The multi-analyte biosensor is portable, inexpensive, and very easy to use and represents an alternative to current detection methods coupled with nucleic acid amplification reactions such as electrochemiluminescence, or those based on more expensive and time consuming methods such as ELISA or tissue culture.

Biosensing Techniques↗
PubMed2001

An investigation into the cyclical incidence of dengue fever.

The purpose of this research was to review the topic of dengue fever transmission and investigate the relationship between seasonal temperature fluctuations and cyclical dengue fever incidence. Data from Puerto Rico (1988-1992) were used to test the model proposed. Dengue fever is a viral disease caused by any one of four antigenically distinct serotypes. It is transmitted by Aedes mosquitoes and infects 80 million people per year. Currently, dengue is endemic in specific tropical and subtropical regions worldwide and epidemic dengue has been reported in the Americas, Asia and some Pacific Islands. Data for Puerto Rico were collected from the NCDC/NOAA and a study conducted by Perez et al. (1994). Multivariate linear regression analysis was used to determine if a relationship exists between the monthly mean temperature lagged and the monthly incidence of dengue fever in Puerto Rico. Statistical significance was achieved and a second-order model produced an R2 of 0.71. A residual analysis reveals positive autocorrelation, thus weakening the model's power to predict monthly dengue incidence. This suggests that other forces or factors related to the history of the herd immunity, the introduction of a new serotype, or demographic transitions are also influencing the cyclical transmission of dengue fever. Case clustering information, regional dengue distributions, and population density transformations must also be obtained in order to assess the forecasting ability of this model. Additional research is needed to avoid oversimplifying the problem. Without such attempts at establishing significant correlations, dengue prevention and control will remain a formidable task for many developing and developed countries.

Aedes↗
PubMed1991

Construction of intertypic chimeric dengue viruses by substitution of structural protein genes.

Dengue virus contains an 11-kilobase positive-strand RNA genome that codes for, in one open reading frame, three structural proteins (capsid, premembrane, and envelope), followed by seven nonstructural proteins. The structural protein genes of a full-length cDNA clone of type 4 dengue virus were replaced with the corresponding genes of dengue 1 or dengue 2 to create intertypic chimeric cDNA. The RNA transcripts made from these templates were infectious when transfected into permissive cells in culture. Progeny of chimeric cDNA produced apparently authentic dengue 1 or dengue 2 structural proteins, together with dengue 4 nonstructural proteins, and as a consequence exhibited type 1 or type 2 serological specificity. Both of the chimeras ultimately grew to the same titer as their type 1 or type 2 parent, but the type 2/type 4 chimera grew very slowly. This chimera also produced small plaques; in contrast, the type 1/type 4 chimera produced normal size plaques. The type 2/type 4 chimera retained the mouse neurovirulence of the dengue 2 virus, which was the source of its structural protein genes. Each of the mice inoculated intracerebrally with the chimera died, but survival time was prolonged. The retardation of replication of the type 2/type 4 chimeric virus suggests that this virus and possibly other intertypic dengue virus chimeras with similar properties should be examined for attenuation in primates and possible usefulness in a live dengue virus vaccine for humans.

Animals↗
PubMed2002

Epidemiology of inapparent and symptomatic acute dengue virus infection: a prospective study of primary school children in Kamphaeng Phet, Thailand.

Dengue viruses are a major cause of morbidity in tropical and subtropical regions of the world. Knowledge about the epidemiology and host determinants of inapparent and severe dengue virus infections is limited. In this paper, the authors report findings from the first 3 years of a prospective study of dengue virus transmission and disease severity conducted in a cohort of 2,119 elementary school children in northern Thailand. A total of 717,106 person-school days were observed from 1998 to 2000. The incidence of inapparent and of symptomatic dengue virus infection was 4.3% and 3.6% in 1998, 3.2% and 3.3% in 1999, and 1.4% and 0.8% in 2000, respectively. Symptomatic dengue virus infection was responsible for 3.2%, 7.1%, and 1.1% of acute-illness school absences in 1998, 1999, and 2000, respectively. The early symptom complex of acute dengue virus infection is protean and difficult to distinguish from other causes of febrile childhood illnesses. The authors' results illustrate the spatial and temporal diversity of dengue virus infection and the burden of dengue disease in schoolchildren in Thailand. Their findings increase understanding of dengue virus transmission and disease severity in a well-defined cohort population and offer a study design in which to test the efficacy of potential dengue vaccines.

Acute Disease↗
PubMed1986

Induction of interferon alpha and gamma from human lymphocytes by dengue virus-infected cells.

Human peripheral blood lymphocytes (PBL) of non-immune donors produced interferon (IFN) when cultured with dengue virus-infected cells. IFN was detected as early as 2 h after exposure of PBL to dengue virus-infected cells, and the titres reached a maximum by 16 h of incubation. Dengue virus-infected cells treated with glutaraldehyde, which produced no infectious dengue virus, also induced IFN. These results indicate that PBL produce IFN in response to dengue virus-infected cells and that the production of IFN by PBL is due to stimulation of PBL by dengue virus-infected cells. Characterization of IFN-producing PBL with monoclonal antibodies demonstrated that the predominant producing cells were contained in M1+ and T3- subsets, and that the Leu11+ subset contains some IFN-producing cells. The IFNs that were produced by the PBL exposed to dengue virus-infected cells were analysed by radioimmunoassay employing monoclonal antibodies specifically to detect IFN-alpha or IFN-gamma. IFN-gamma as well as IFN-alpha was produced by PBL exposed to dengue virus-infected cells. Both IFN-alpha and IFN-gamma were predominantly produced by PBL contained in M1+ and T3- subsets. The observation that PBL of non-immune donors produced IFN-gamma as well as IFN-alpha in response to dengue virus-infected cells is of interest in view of the immunoregulatory roles of IFNs and the hypothesis that the complications of dengue virus infection (haemorrhagic fever and shock) may be due to immunopathology.

Antibodies, Monoclonal↗
PubMed1989

Dengue virus-specific murine T-lymphocyte proliferation: serotype specificity and response to recombinant viral proteins.

Definition of the T-lymphocyte responses to dengue viruses should aid in the development of safe and effective vaccines and help to explain the pathophysiology of dengue hemorrhagic fever and dengue shock syndrome. In this study, we demonstrated that dengue virus-specific T lymphocytes were detected in spleen cells from dengue virus-immune mice using an in vitro proliferation assay. Following immunization with a single dose of infectious dengue virus, murine lymphocytes showed increased proliferation when incubated in the presence of viral antigens of the same serotype but not in the presence of control antigens. Depletion experiments with antibody and complement showed that the population of responding cells expressed the Thy1+ L3T4+ Lyt2- phenotype. This indicates that the predominant proliferating cells are T lymphocytes of the helper-inducer phenotype. Dengue virus-specific memory lymphocyte responses were detectable for at least 22 weeks after immunization. The response to primary infection was primarily serotype specific, with some serotype cross-reactivity present at a low level. We demonstrated that lymphocytes from mice immunized with dengue 4 virus proliferate in response to a combination of dengue 4 virus C, pre-M, E, NS1, and NS2a proteins expressed in Sf9 cells with a recombinant baculovirus, and, to a lesser extent, to the dengue 4 virus E protein alone.

Animals↗
PubMed1996

Multiple specificities in the murine CD4+ and CD8+ T-cell response to dengue virus.

The target epitopes, serotype specificity, and cytolytic function of dengue virus-specific T cells may influence their theoretical roles in protection against secondary infection as well as the immunopathogenesis of dengue hemorrhagic fever. To study these factors in an experimental system, we isolated dengue virus-specific CD4+ and CD8+ T-cell clones from dengue-2 virus-immunized BALB/c mice. The T-cell response to dengue virus in this mouse strain was heterogeneous; we identified at least five different CD4+ phenotypes and six different CD8+ phenotypes. Individual T-cell clones recognized epitopes on the dengue virus pre-M, E, NSl/NS2A, and NS3 proteins and were restricted by the I-Ad, I-Ed, Ld, and Kd antigens. Both serotype-specific and serotype-cross-reactive clones were isolated in the CD4+ and CD8+ subsets; among CD8+ clones, those that recognized the dengue virus structural proteins were serotype specific whereas those that recognized the nonstructural proteins were serotype cross-reactive. All of the CD8+ and one of five CD4+ clones lysed dengue virus-infected target cells. Using synthetic peptides, we identified an Ld-restricted epitope on the E protein (residues 331 to 339, SPCKIPFEI) and a Kd-restricted epitope on the NS3 protein (residues 296 to 310, ARGYISTRVEM GEAA). These data parallel previous findings of studies using human dengue virus-specific T-cell clones. This experimental mouse system may be useful for studying the role of the virus serotype and HLA haplotype on T-cell responses after primary dengue virus infection.

Animals↗
PubMed2005

Dengue virus inhibits alpha interferon signaling by reducing STAT2 expression.

Alpha/beta interferon (IFN-alpha/beta) is a key mediator of innate antiviral responses but has little effect on the established replication of dengue viruses, which are mosquito-borne flaviviruses of immense global health importance. Understanding how the IFN system is inhibited in dengue virus-infected cells would provide critical insights into disease pathogenesis. In a recent study analyzing the ability of individual dengue virus-encoded proteins to antagonize the IFN response, nonstructural (NS) protein 4B and possibly NS2A and NS4A were identified as candidate IFN antagonists. In monkey cells, NS4B appeared to inhibit both the IFN-alpha/beta and IFN-gamma signal transduction pathways, which are distinct but overlapping (J. L. Munoz-Jordan, G. G. Sanchez-Burgos, M. Laurent-Rolle, and A. Garcia-Sastre, Proc. Natl. Acad. Sci. USA 100:14333-14338, 2003). For this study, we examined the effects of dengue virus on the human IFN system, using cell lines that were stably transfected with self-replicating subgenomic dengue virus RNA (replicons) and that expressed all of the dengue virus nonstructural proteins together. We show here that in replicon-containing cells dengue virus RNA replication and the replication of encephalomyocarditis virus, an IFN-sensitive virus, are resistant to the antiviral effects of IFN-alpha. The presence of dengue virus replicons reduces global IFN-alpha-stimulated gene expression and specifically inhibits IFN-alpha but not IFN-gamma signal transduction. In cells containing replicons or infected with dengue virus, we found reduced levels of signal transducer and activator of transcription 2 (STAT2), which is a key component of IFN-alpha but not IFN-gamma signaling. Collectively, these data show that dengue virus is capable of subverting the human IFN response by down-regulating STAT2 expression.

Cell Line↗
PubMedDate not supplied

Dengue Fever in travelers returning from southeast Asia.

BACKGROUND: Dengue fever is an important illness facing travelers from nonendemic to endemic countries. METHODS: We reviewed 696 consecutive returned travelers managed at an Australian tertiary-care hospital for an illness acquired overseas. Patients with dengue fever were compared to those with a dengue-like illness, malaria, typhoid fever and rickettsial infections. RESULTS: In total, 19 cases of dengue fever and 20 cases of dengue-like illness were diagnosed, with 85% of cases acquired in Asia. The most common presenting features of dengue were fever (100%), myalgia (79%), rash (74%), headache (68%), nausea (37%), and diarrhea (37%). Compared to those with malaria, typhoid fever and rickettsial infections, patients with dengue were significantly more likely to have myalgia and a temperature <39 degrees C. Compared to all other illnesses in our returned travelers, dengue fever was 18 times more likely if fever and leukopenia were present, 71 times if fever and rash were present, and 230 times if fever, rash and leukopenia were present. All patients with dengue recovered completely. CONCLUSIONS: Dengue fever is an important health problem for travelers not only to Southeast Asia but to all endemic countries. The prevalence appears to be increasing in travelers, and health care professionals need to be familiar with its presentation in travelers. The clinical presenting features provide important guides to establishing the diagnosis.

Adolescent↗