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PubMedDate not supplied

Distribution of dengue and Japanese encephalitis among children in rural and suburban Thai villages.

In the rainy season of 1989, IgG and IgM antibodies against dengue and Japanese encephalitis viruses (measured by enzyme-linked immunoassay [ELISA]) in serum from all primary-school children in two areas of central Thailand were sampled in order to choose a study site for more detailed epidemiological and entomological analysis. Students in three schools in the largely non-agricultural, suburban community of Bang Bua Thong, Nontaburi Province were sampled in late June and July. Of 1,477 children, 33/1,000 had recent dengue infection and 7/1,000 had recent JE infection. The rate of dengue infection in each village influenced the rate in schools, in that the rate of the school could be predicted from the proportion of students coming from each village. This result suggested that most transmission occurred in the residential environment; otherwise, the rate in each village going to a single school would be identical. Serum samples were taken in late August in the agricultural community of Hua Samrong, Chachoengsao Province. Of 748 students in two schools, 95/1,000 had signs of recent dengue infection and 32/1,000 had signs of recent JE infection. Two of 12 villages had significantly less flavivirus infection than some other villages and three villages had significantly more flavivirus infection. The children from one village had a dengue infection rate of 256 per 1,000, which was higher than the national average for the worst year (1987) previously recorded in Thailand. Within Hua Samrong, there was evidence for significant dengue transmission in one of the schools and concentrated transmission in small areas of two of the villages. The younger age group (3-8 years old) had significantly higher risk of infection by either flavivirus than older children. Elevated homes with wooden floors had significantly higher risk of dengue in the largest village. The observations from 1989 describe the epidemiological situation in rapidly developing, rural villages. This stage of development is probably being repeated throughout Southeast Asia as formerly isolated, rural villages become connected by transportation and economy to urban centers. What appears to be a single dengue outbreak based on passive surveillance conducted on a regional basis may actually be a variety of epidemiological situations. The practical implication of this conclusion is that application of a combination of vaccination and vector control should be targeted to higher risk areas in order to increase the likelihood of regional dengue virus eradication.

Adolescent↗
PubMed2001

Plasma concentrations of sVCAM-1 and severity of dengue infections.

Adhesion molecules are essential for the immune response. They are involved in the regulation of cell-to-cell contact, thereby enabling leukocytes to communicate. Circulating forms of adhesion molecules are found in the serum of healthy individuals. Raised levels have been associated with disease severity in HCV and other infections and thus appear to be good markers of endothelial damage. The levels of soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) and of sP and sL-selectin in the plasma of children hospitalised for dengue in French Polynesia were monitored. Studies from the 1996/1997 dengue-2 outbreak, showed that levels of sVCAM-1 increase steadily during the febrile period, peak on day 7, and then decline relatively rapidly. Disregarding the time frame within the febrile period, sVCAM-1 levels were always higher compared to controls. There was a significant association between sVCAM-1 levels and dengue haemorrhagic fever, a severe manifestation of dengue virus infection characterised by plasma leakage. No association was apparent between sVCAM-1 levels and primary vs. secondary dengue virus infections. Levels of sP-selectin and sL-selectin were significantly higher in primary compared with secondary infection but were not different in patients presenting with plasma leakage. Lastly, sVCAM-1 levels were significantly higher in an outbreak of severe disease in 1989/1990 (dengue-3) when compared to a non-severe outbreak in 1988/1989 (dengue-1) and a mild outbreak in 1996/1997 (dengue-2). The results suggested that levels of sVCAM-1 production might prove to be a useful marker in the management of severe dengue.

Biomarkers↗
PubMed2002

Imported dengue--United States, 1999 and 2000.

Dengue is a mosquito-transmitted acute viral illness caused by any of the four dengue virus serotypes (DEN-1, DEN-2, DEN-3, and DEN-4). Dengue is endemic in most tropical and subtropical areas of the world and has occurred among U.S. residents returning from travel to such areas. CDC maintains a laboratory-based passive surveillance system for imported dengue among U.S. residents (laboratory-diagnosed dengue in a U.S. resident living in an area without known authochthonous dengue transmission, with travel history outside the United States in the 14 days before symptom onset). The system relies on reports by clinicians to state health departments, which forward patient specimens to CDC for diagnostic testing. This report summarizes information about imported dengue cases among U.S. residents during 1999-2000. The findings indicate that dengue continues to cause disease in U.S. travelers abroad. Travelers to tropical areas should protect themselves from mosquito bites, and health-care providers should consider dengue in the differential diagnosis of illness for patients who have returned recently from such areas.

Adolescent↗
PubMed2003

Seroepidemiological survey among schoolchildren during the 2000-2001 dengue outbreak of Ratchaburi Province, Thailand.

From August 2000 to 2001, a dengue outbreak occurred in Mueang district, Ratchaburi Province, Thailand. About 800 cases of dengue infection were reported, and among them, 49.5% were clinically diagnosed as dengue hemorrhagic fever according to the WHO criteria. During the outbreak, the incidence rate of dengue infection in Hin Gong subdistrict was 2.9 per 1,000 population. A seroepidemiological survey was conducted among primary schoolchildren from July 2000 to June 2001, to monitor dengue transmission. In a baseline survey, 283 children were surveyed for dengue antibody and 71% were IgG seropositive. In June 2001, the rate of dengue infection showed an increase of 8.8% with 8.0% among immune children and 10.3% among naive schoolchildren. Among 283 schoolchildren, 90 were followed up 3 times, in September and December 2000, and June 2001. An increase in the rate of seroconversion was observed in the period September to December 2000, while the peak dengue outbreaks in the dry season occurred in February 2001. Serosurveys among schoolchildren appear to be early warning system, and can be advantageous in early dengue control actions, in order to break the chain of transmission before an impending epidemic.

Antibodies, Viral↗
PubMed2005

Endoscopic findings and management of dengue patients with upper gastrointestinal bleeding.

There are 100 million cases of dengue infection, 500,000 cases of dengue hemorrhagic fever, and 25,000 deaths annually due to dengue worldwide. Gastrointestinal bleeding is the most common type of severe hemorrhage in dengue fever. However, there are no reports about the clinical applications of endoscopic therapy for upper gastrointestinal bleeding (UGI) in dengue patients. From June 17, 2002 to January 30, 2003, 1,156 patients with confirmed dengue virus infection were treated at Kaohsiung Chang Gung Memorial Hospital in Taiwan. We analyzed those patients who had received endoscopic therapy for UGI. The characteristic endoscopic findings, therapeutic courses, and amount of blood component transfused were collected from their charts for statistical analysis. Among the 1,156 dengue patients, 97 (8.4%) had complications of UGI bleeding during hospitalization. The endoscopic findings included hemorrhagic (and/or erosive) gastritis in 67% of the patients, gastric ulcer in 57.7%, duodenal ulcer in 26.8%, and esophageal ulcer in 3.1%. Of the 73 patients with peptic ulcer, 42 (57.5%) met the endoscopic criteria (recent hemorrhage) for endoscopic hemostasis therapy. Peptic ulcer patients with recent hemorrhage required more transfusions with packed red blood cells (P = 0.002) and fresh frozen plasma (P = 0.05) than those without recent hemorrhage. Among these 42 patients with recent hemorrhage, endoscopic injection therapy was conducted in 15 patients (group A). The other 27 patients (group B) did not receive endoscopic therapy. After endoscopy, patients in group A required more transfusions with packed red blood cells (P = 0.03) and fresh frozen plasma (P = 0.014) than did patients in group B. There were no significant differences between groups A and B in duration of hospital stay and amounts of transfused platelet concentrate after endoscopy. Medical treatment with blood transfusion is the mainstay of management of UGI bleeding in dengue patients. Patients having peptic ulcer with recent hemorrhage require more transfusions with packed red blood cells and fresh frozen plasma for management of UGI bleeding than those without recent hemorrhage. However, when peptic ulcer with recent hemorrhage is encountered during the endoscopic procedure, endoscopic injection therapy is not an effective adjuvant treatment of hemostasis in dengue patients with UGI bleeding.

Adult↗
PubMed1982

Serological studies on a case of laboratory dengue infection.

One of the authors (Y.O.), who had previously been immunized with Japanese encephalitis (JE) vaccine, showed symptoms of typical dengue fever 6 days after accidental infection with a newly isolated dengue type 4 virus strain from a patient with dengue hemorrhagic fever (DHF) in Thailand. His sera were examined by hemagglutination inhibition (HI), complement fixation (CF) and neutralization (N) tests. The JE N antibody titers of his sera were high even on the first day of the illness and remained almost constant during the next year. Antibodies that reacted with dengue viruses were detected from a very early stage of the illness by all three serological tests. In addition, his convalescent phase sera showed high titers against all 4 types of dengue virus. These data suggest that the dengue infection caused secondary stimulation of antigens of flavivirus. Sedimentation analysis of antibodies in Y.O.'s serum (day 9) was carried out and IgM antibody that reacted only with dengue type 4 virus and homologous infecting virus was separated. These findings clearly demonstrated that the laboratory infection of Y.O. was primary dengue infection with dengue type 4 virus.

Antibodies, Viral↗
PubMed1994

Dengue in the Western Hemisphere.

Dengue is an important insect-borne viral disease, transmitted in the Western hemisphere by the A. aegypti mosquito. It is endemic in the Caribbean with sporadic outbreaks in different regions. Cases in the United States are mostly imported cases but can be seen in the Gulf states as well as the Southeast. Dengue is most frequently a self-limiting illness characterized by sudden onset of fever, chills, headache, retroocular pain, general malaise, myalgias, arthralgias, and a skin rash. In a small group of patients, the same viruses may cause dengue hemorrhagic fever and dengue shock syndrome. In the Western hemisphere, dengue with hemorrhagic manifestations and dengue with shock syndrome have been documented frequently in adults. There are four serotypes of dengue viruses and all have been documented to be present in the Western hemisphere. The clinical illness is similar for any of the four serotypes; after infection there is lifelong homotypic immunity and heterotypic immunity for several months. The diagnosis of dengue is based on clinical findings and can be confirmed by serologic tests or virus isolation. There is no specific treatment for dengue; hydration is important as well as aggressive fluid management if hypotension develops. It is important to avoid aspirin and salicylates. The best treatment is prevention through mosquito control and public education to eradicate the breeding grounds for the mosquito.

Animals↗
PubMed1996

Dengue hemorrhagic fever.

Dengue has been known for more than 200 years. The first dengue viruses were isolated about 50 years ago. Prior to the 1950's, dengue was considered a mild febrile disease, though rare hemorrhagic and fatal cases were known to occur. After that date, the first epidemics of dengue hemorrhagic fever (DHF) appeared in Southeast Asia, and DHF became the most important cause of childhood morbidity and mortality in the region. The emergence of DHF epidemics was first explained by mutations affecting dengue viruses, making them more virulent, but this hypothesis was not retained. Then, the "secondary infection" or "immune enhancement" theory was proposed to explain the increased virulence of dengue viruses when children had a secondary infection. This second hypothesis is still actually favoured. However, observations in Southeast Asia, some Pacific islands, and Americas do not agree with the "secondary infection" hypothesis, which consequently has been modified several times. Recent advances in molecular biology have led to the recognition that some viral strains are more virulent than others. Another hypothesis is the selection of more virulent dengue strains by the new vector Ae. aegypti, replacing the local vector Ae. albopictus, when urbanization and modern transportation increased in Southeast Asia after the last war. Comparisons between epidemics are very difficult, because of the distinction between DHF cases according to WHO criteria and dengue fever (DF) cases with hemorrhages. This distinction has no pathogenic or prognostic grounds, and makes the task of clinicians more difficult. The actual situation in countries facing dengue epidemics makes clear that this disease will continue to be a public health problem for some time to come.

Asia, Southeastern↗
PubMed2006

[Low concordance between early clinical suspicion of dengue and its serological confirmation].

BACKGROUND: Early detection of dengue could help to prevent its complications. The usefulness of clinical criteria for diagnosis of the disease must be ascertained. AIMS: To assess the correlation between laboratory and clinical diagnosis of dengue, done during the first consultation in the emergency room. To estimate the impact of clinical diagnosis on the initial medical treatment. PATIENTS AND METHODS: Patients older than 5 years with an acute febrile syndrome that consulted during the first 72 hours of disease, during 2004, at an emergency room in Bucaramanga, Colombia, were studied. Symptoms and the clinical diagnosis of the initial evaluation were registered. Paired serum samples for dengue specific ELISA-IgM test and viral isolation were obtained. The association of the initial clinical diagnosis with early symptoms, initial medical treatment and laboratory diagnosis was evaluated. RESULTS: One hundred sixty eight patients were enrolled (54 with confirmed dengue infection). Clinical diagnosis of dengue was associated to a higher request of complete blood counts (p = 0.01) and greater use of intravenous fluids (p = 0.02). However, clinical diagnosis was not correlated with the laboratory diagnosis (p = 0.15). The percentage of agreement was less than would be expected by chance (Kappa = -0.1). Headache was associated to the initial clinical diagnosis of dengue (p = 0.03), and only metrorrhagia was associated with confirmed dengue infection (p = 0.04). CONCLUSIONS: The early clinical suspicion of dengue has a low concordance with the laboratory confirmation of the disease.

Adolescent↗
PubMed2006

Severe dengue: the need for new case definitions.

Dengue fever imposes a societal burden that is difficult to measure because of the disease's non-specific symptoms and the lack of easily applied case definitions for its more severe manifestations. An efficacy trial of a tetravalent vaccine is expected in the near future, but only one of the severe dengue syndromes-the continuum of dengue haemorrhagic fever and dengue shock syndrome-is well defined. One of the results of the focus on dengue haemorrhagic fever is the false perception of low disease burden in the Americas, which is an obstacle to the mobilisation of political and economic resources to fight the disease. Three improvements are necessary to standardise the dengue haemorrhagic fever definition and to allow it to do well in different populations: (1) redefine the threshold for thrombocytopenia, (2) clarify the standard practice and value of the tourniquet test, and (3) incorporate a criterion to measure intravenous fluid replacement. In addition, for an accurate estimation of dengue burden, locally appropriate definitions of severe dengue must be devised and standardised so they will be considered valid in the global research community.

Cost of Illness↗
PubMed2000

Participation of the Dengue virus in the fibrinolytic process.

To date, the phatophysiology of hemorrhagic dengue is still unknown and hypotheses which aim to explain the unfortunate cases of the disease (hemorrhagic fever/shock syndrome) are based on epidemiological data and favor the notion of the participation of heterotypic non-neutralizing antibodies during the course of secondary infection (immunologic status of the host). However, cases of hemorrhagic dengue have been reported during the course of primary infections. We propose that the dengue virus, specifically the envelope glycoprotein can participate directly in the installation of the hemorrhagic phenomenon by means of the binding and activation of plasminogen (PLG) as condition previous to the development of the fibrinolytic process. Based on this hypothesis, we evaluated the biological activity of some viral isolates proceeding from hemorrhagic and from dengue fever cases in an in vitro model of fibrinolysis. Dengue isolates were capable of activating PLG. The plasmin generated specifically degraded the fibrin/fibrinogen molecule. This catalytic process can be prevented by the presence of the specific plasmin inhibitor, alpha-2-antiplasmin, for virus isolates from dengue fever, but not for isolates associated with dengue hemorrhagic disease, favoring the exacerbation of the fibrinolytic activity. This new approach allows us to suggest the importance of viral factors in the dengue hemorrhagic fever.

Amino Acid Sequence↗
PubMed1998

Exploratory space-time analysis of reported dengue cases during an outbreak in Florida, Puerto Rico, 1991-1992.

The spatial and temporal distributions of dengue cases reported during a 1991-1992 outbreak in Florida, Puerto Rico (population = 8,689), were studied by using a Geographic Information System. A total of 377 dengue cases were identified from a laboratory-based dengue surveillance system and georeferenced by their residential addresses on digital zoning and U.S. Geological Survey topographic maps. Weekly case maps were generated for the period between June and December 1991, when 94.2% of the dengue cases were reported. The temporal evolution of the epidemic was rapid, affecting a wide geographic area within seven weeks of the first reported cases of the season. Dengue cases were reported in 217 houses; of these 56 (25.8%) had between two and six reported cases. K-function analysis was used to characterize the spatial clustering patterns for all reported dengue cases (laboratory-positive and indeterminate) and laboratory-positive cases alone, while the Barton and David and Knox tests were used to characterize spatio-temporal attributes of dengue cases reported during the 1991-1992 outbreak. For both sets of data significant case clustering was identified within individual households over short periods of time (three days or less), but in general, the cases had spatial pattern characteristics much like the population pattern as a whole. The rapid temporal and spatial progress of the disease within the community suggests that control measures should be applied to the entire municipality, rather than to the areas immediately surrounding houses of reported cases. The potential for incorporating Geographic Information System technologies into a dengue surveillance system and the limitations of using surveillance data for spatial studies are discussed.

Adolescent↗
PubMed2005

[Development of multiplex reverse translation-polymerase chain reaction methods for detection of dengue virus type 1-4 and its application in clinical use].

OBJECTIVE: To develop multiplex reverse translation-polymerase chain reaction (RT-PCR) method for detection of dengue virus type 1-4. METHODS: Based on the genomes sequence analysis of dengue virus type 1-4, four-pair of primers were designed. The specificity of the primers was primarily tested by searching the GenBank DNA sequence database. The optimal reaction conditions of the multiplex RT-PCR were then established. The specificity of RT-PCR was tested using the homologous yellow fever virus and Japanese encephalitis virus. 30 serum samples of dengue virus from suspected sufferers in the prevalence of dengue virus in 2003 were detected using the methods we developed. RESULTS: Positive segments about 295, 237, 118, 347 bp could be seen in the multiplex RT-PCR production of dengue virus type 1-4, respectively. There were no positive segments in the RT-PCR productions of Japanese encephalitis virus and yellow fever virus. 25 of the 30 serum samples showed dengue virus type 1 positive results, while the sequencing results suggesting the amplification sequence having a high homology with dengue virus type 1 strain Cambodia, GD14/97 and GD05/99 (97%, 97%, 98%, respective). CONCLUSION: The method of multiplex RT-PCR we established could be used for early detection and identification of dengue virus type 1-4.

Base Sequence↗
PubMed2003

Correlation between increased platelet-associated IgG and thrombocytopenia in secondary dengue virus infections.

Although the public health impact of dengue is increasing rapidly, the mechanism of thrombocytopenia in this disease remains unknown. To elucidate this mechanism, the relationship between platelet-associated IgG (PAIgG) and platelet count in 53 patients in the acute phase of secondary dengue virus infection was investigated in a prospective-hospital-based study. A significant inverse correlation between the two parameters was found in these patients, while no correlation was observed in healthy volunteers. The low baseline platelet counts during the acute phase in 12 patients with secondary dengue virus infection significantly increased during the convalescent phase, while the increased PAIgG levels during the acute phase in these patients significantly decreased during the convalescent phase. Anti-platelet IgG autoantibody was detected rarely in the plasma of 53 patients with secondary dengue infection. The involvement of anti-dengue virus IgG was also shown in platelets from all of 8 patients in the acute phase of secondary dengue virus infection. These findings suggest that PAIgG formation involving anti-dengue virus IgG plays a pivotal role in the induction of transient thrombocytopenia during the acute phase of secondary dengue virus infection.

Acute Disease↗
PubMed2004

Lymphocyte activation and hepatic cellular infiltration in immunocompetent mice infected by dengue virus.

Activation and expansion of dengue virus-specific T cells and abnormal liver functions in dengue patients have been documented. However, it remains to be determined whether T cells are involved in the pathogenic mechanism of dengue virus infection. In this study, immunocompetent C57BL/6 mice were employed to study dengue virus-induced T cell activation. Mice were inoculated with 10(8) PFU dengue virus serotype 2 strain 16681 by the intravenous route. Dengue viral core RNA was detected by RT-PCR in mouse serum, liver, spleen, and brain at different time points after infection. Splenic T cells were activated as evidenced by their expression of CD69 and O-glycosylated CD43 at as early as day 3 after infection. Splenic T cell expression of O-glycosylated CD43 and IFN-gamma production coordinately peaked at day 5. Coincided with the peak of splenic T cell activation was hepatic lymphocyte infiltration and elevation of liver enzymes. Flow cytometric analysis revealed the infiltrating CD8(+) T cell to CD4(+) T cell ratio was 5/3. After a second inoculation of dengue virus, hepatic T cell infiltration and liver enzyme levels increased sharply. The infiltrating hepatic CD8(+) T cell to CD4(+) T cell ratio increased to 5.8/1. A strong correlation was found between T cell activation and hepatic cellular infiltration in immunocompetent mice infected with dengue virus. The kinetics of liver enzyme elevation also correlated with that of T cell activation. These data suggest a relationship between T cell infiltration and elevation of liver enzymes.

Alanine Transaminase↗
PubMed2005

Elevated plasma levels of the long pentraxin, pentraxin 3, in severe dengue virus infections.

C-reactive protein is one of the most widely used indicators of the response of acute-phase proteins. The measurement of C-reactive protein in dengue, however, is clinically not useful, because of marginally elevated levels and absent association with disease severity. The prototypic long pentraxin, pentraxin 3, is an acute phase protein that is structurally related but distinct from C-reactive protein which has proven to correlate with the severity of bacterial infection in critically ill patients. The potential involvement of pentraxin 3 in dengue and its aptitude to predict more severe disease or poor clinical outcome has not been studied previously. We therefore measured pentraxin 3 plasma levels in 44 dengue virus infected patients. Pentraxin 3 levels were strikingly higher when compared to C-reactive protein levels, with highest pentraxin 3 values observed in the first 7 days after the onset of symptoms. Median pentraxin 3 levels at admission and peak levels during follow up were higher in patients suffering from dengue shock syndrome (at admission: 119.3 ng/ml [interquartile range 61.8--188.7], peak values during follow up: 147.9 ng/ml [interquartile range 85.7--204.3]) compared to levels found in patients with dengue fever and dengue hemorrhagic fever (at admission: 59.0 ng/ml [interquartile range 28.6--100.3], P=0.040; peak values during follow up: 80.8 ng/ml [interquartile range 36.1--168.1], P=0.020). Our results indicate that pentraxin 3 seems to be a marker of infection better than C-reactive protein in dengue. The role of pentraxin 3 in the pathogenesis of dengue and its potential as an early prognostic indicator of disease severity needs further assessment.

C-Reactive Protein↗
PubMed2000

Complete genomic sequence of a dengue type 2 virus from the French West Indies.

Severe forms of dengue fever, dengue haemorrhagic fever, and dengue shock syndrome, were not prominent in the Americas until the epidemic of Cuba in 1981. Since that time, they have spread to other countries in Central and South America, correlating with the spread of dengue type 2 viruses related to Southeast Asian strains. We report here the complete genomic sequence of a dengue type 2 virus isolated during the epidemic in La Martinique in 1998. This constitutes the first complete genetic characterization of a dengue virus strain from French West Indies, and also the first molecular identification in this region of a dengue 2 strain phylogenetically related to the emerging American type 2 dengue viruses.

Amino Acid Substitution↗
PubMed1989

Serologically defined linear epitopes in the envelope protein of dengue 2 (Jamaica strain 1409).

Antisera from dengue patients and dengue virus infected rabbits recognized octapeptides corresponding to linear amino acid sequences in the envelope protein of dengue 2 (Jamaica 1409). Although no peptide was recognized by sera from all dengue infected hosts, two peptides (216LPLPWLPG223 and 448FSGVSWTM455) were recognized by sera from all dengue 2 infected rabbits. One of these 448FSGVSWTM455 was also recognized by sera from both the dengue 2 patients tested. No peptides were identified which reacted exclusively with all dengue 2 infected animals. Use of a mouse monoclonal antibody (1B7) enabled identification of two regions (50AKQPATLR57 and 127GKVVLPEN134) and possibly a third (349GRLITVNP356) in the envelope protein of dengue 2 likely to be involved in haemagglutination inhibition and virus neutralization in vitro.

Amino Acid Sequence↗