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Serologic evidence for an epizootic dengue virus infecting toque macaques (Macaca sinica) at Polonnaruwa, Sri Lanka.

Dengue is one of the most rapidly emerging diseases in the tropics. Humans are the principal reservoir of dengue viruses. It is unclear if nonhuman primates also serve as a reservoir of human dengue viruses under certain conditions. In this study, a cross-sectional serologic survey was carried out to characterize the pattern of transmission of a recently identified dengue virus among toque macaques in Sri Lanka. The results indicated that an epizootic dengue virus was active among the macaques. A single epizootic had taken place between October 1986 and February 1987 during which 94% of the macaques within the 3 km2 study site were exposed to the virus. The epizootic was highly focal in nature because macaques living 5 km from the study population were not exposed to the virus. The transmission of dengue viruses among macaques in the wild may have important public health implications.

Animals↗

Referral pattern of leptospirosis cases during a large urban epidemic of dengue.

During heavy seasonal rainfall in 1996, concurrent epidemics of dengue and leptospirosis occurred in an urban center in northeastern Brazil. We interviewed 110 cases of leptospirosis hospitalized a median of seven days after the onset of illness to evaluate the impact of the dengue epidemic on the triage of suspected leptospirosis from ambulatory clinics to the infectious disease reference hospital. Within the first three days of illness, 46 (42%) cases sought their first medical evaluation, and 28 (61% of 46) received a diagnosis of dengue. Dengue diagnoses were associated with a median of five days delay in referral to the infectious disease hospital. Patients who reported initial diagnoses of dengue were more likely than other patients to have required admission to the intensive care unit (odds ratio [OR] = 2.7, 95% confidence interval [CI] = 0.8-9.5) and to have died during hospitalization (OR = 5.1, 95% CI = 0.8-55.0). These findings indicate that diagnostic confusion between the early symptoms of leptospirosis and dengue may have contributed to the high mortality observed during the leptospirosis epidemic.

Adolescent↗

[Dengue fever with neurologic expression. Three cases in adults].

Dengue fever, unlike most other arboviral diseases, does not usually cause encephalitis. However, neurologic symptoms with poor prognosis have been regularly reported, mostly in Asian children affected by the severe dengue hemorrhagic fever/dengue shock syndrome, and attributed to a non specific, anoxic or metabolic encephalopathy. Recently, first isolations of dengue viruses from CSF or brain tissue, have renewed this concept. We report 3 dengue fever cases with neurologic manifestations and favorable outcome. Occurrence in adult age, during classic (benign) dengue fever (2 cases), and neurologic sequellae (1 case) were the three outstanding features. We point out the proteiform expression of these neurologic changes and their low incidence rate (< 3% in our series of adult dengue fever). Although their pathogenesis is poorly understood, different mechanisms are suggested: encephalopathy (case n. 1), acute specific encephalitis (questionable in case n(o) 2), or post-infective encephalitis (case n(o) 3).

Adult↗

[Epidemiologic surveillance of dengue fever: non specific alert system in the hospital milieu in Cayenne].

A retrospective study was carried out in the General Hospital of Cayenne, the main city in French Guiana, where malaria is endemic and dengue fever constitutes a permanent threat. The aim of this study was to test an alert system for epidemic outbreaks of dengue fever. Patients attending the emergency ward and for whom a search of Plasmodium was prescribed were included. In 90% of cases, patients were febrile, presenting clinical symptoms compatible with malaria or dengue fever-like syndrome. The period of survey covered 39 months (January 1996 to March 1999). Three indices were studied; two non specific: EMN (Emergency Malaria Negative--UPN in French): number of negative malaria blood tests for patients having consulted the emergency ward; EMNT (Emergency Malaria Negative Thrombopenia--UPNT in French): UPN with platelets < 150.000; and one more specific; number of hospitalised dengue fever cases according to data from a hospital programme on medical systems information. EMN weekly follow-ups led to three epidemic alerts, two of which turned out to be crucial for dengue. Accounting for thrombopenia (EMNT) reinforced the specificity. This simple and reactive alert system should incite increased serological and virological surveillance and contribute to precocious antivectorial control measures in districts where several dengue fever cases are suspected.

Dengue↗

[Imported dengue hemorrhagic fever: aprops of 1 case presenting with signs of acute alithiasic cholecystitis].

Dengue is prevalent in all subtropical areas. Hemorrhagic forms of the disease were first described in southeast Asia but have now been observed on several continents. Travelers are at risk for infection and the likelihood of imported dengue has grown in relation to volume of air traffic. In developed countries, dengue usually presents in the benign form, but sudden aggravation is always possible. The purpose of this report is to describe a case of imported dengue hemorrhagic fever associated with abdominal pain in a traveler returning from Asia. Radiological findings were suggestive of nonlithiasic cholecystitis. Similar ultrasound feature have been reported by pediatric groups during dengue outbreaks in Asia. Previous findings have shown that bladder involvement is a predictive sign of severe disease and impending shock. Surgery is contraindicated in these patients. Close clinical and laboratory surveillance is necessary due to the high risk of aggravation. The pathogenesis of this severe life-threatening form of the disease is unclear. A possible explanation is involvement of a more virulent strain of virus. Dengue should always be considered after malaria in the differential diagnosis of returning travelers patients presenting fever.

Abdominal Pain↗

Evaluation of the plasma kinin system in dengue hemorrhagic fever.

The role of the plasma kinin system in the pathogenesis of dengue hemorrhagic fever (DHF) ws explored by simultaneously measuring factor XLL (Hageman), prekallikrein, kallikrein inhibitors, bradykinin, and complement (C3) in the blood of Thai children with DHF and acute febrile illnesses other than dengue. Prekallikrein, factor XII, and C3 levels were significantly lower in DHF patients compared to fever control patients with the lowest mean levels found in dengue patients with shock. However, bradykinin concentrations were not elevated and mean activity levels of kallikrein inhibitors were not depressed in dengue patients. Two dengue patients first studies at least 2 days before onset of shock had falling C3 levels which were more closely related temporally to the onset of shock than were their rising levels of prekallikrein. The results fail to provide convincing evidence ofr activation of the plasma kinin system leading to free bradykinin or a significant role for bradykinin in the immunopathogenesis of DHF. By contrast, the results refocus attention on complement as a potentially important humoral mediator of the dengue shock syndrome.

Antigens, Viral↗

Dengue fever risk and prevention for short-term group travelers to tropical regions.

The purpose of this study is to describe dengue fever infections in a group traveling from northern Louisiana to Mexico. Of 50 travelers in the group, three adolescents aged 15-16 developed febrile symptoms a few days after returning. Clinical diagnosis suggested dengue fever. Serum samples were obtained from the three adolescents and from 19 of the adults (age 18 and older) who were in the group. The samples were analyzed by the Centers for Disease Control using dengue IgM capture enzyme linked immunosorbant assay. Results confirmed the three symptomatic adolescents and five asymptomatic adults had been infected with the Flaviviridae virus that causes dengue. We conclude that since there is no vaccine to prevent dengue infections, travelers to high-risk areas should take steps to prevent infection and that clinicians encountering patients with febrile illnesses after travel to such regions should consider a diagnosis of dengue fever.

Adolescent↗

Comparison of IgM capture ELISA with a commercial rapid immunochromatographic card test & IgM microwell ELISA for the detection of antibodies to dengue viruses.

BACKGROUND & OBJECTIVES: There is a need for a reliable test for the early diagnosis of dengue fever (DF), which is now active in many parts of India especially in the post monsoon months. This study evaluated two commercial tests with an assay available from a national laboratory in India to obtain information and to make a comparison among the three tests as to which will be the most suited for the detection of IgM antibodies to dengue virus. METHODS: An IgM capture ELISA (National Institute of Virology, Pune, India) was compared with two commercial tests, the PanBio Rapid Immunochromatographic Card Test (Brisbane, Australia) and the PanBio Microwell IgM ELISA for the detection of IgM antibodies to dengue virus. We tested 154 samples from individuals with febrile illnesses having DF--like symptoms. RESULTS: The NIV IgM capture ELISA (MAC-ELISA) showed a high positivity rate (38.9%) as compared to the PanBio Rapid (22.7%) and the PanBio IgM ELISA (20.7%). The true prevalence of disease, sensitivity and specificity of the three tests were estimated using 2LC latent class models using expectation-maximization (EM) algorithm. The NIV MAC-ELISA showed a high sensitivity (96%) as compared to PanBio Rapid (73%) and PanBio IgM ELISA (72%). A subset of 68 samples (of the 154 tested) were analyzed by the NIV MAC-ELISA for IgM antibodies additionally to Japanese encephalitis (JE) and West Nile (WN) of which 31 samples showed positivity to either one, two or all three flaviviruses. Out of the 8 samples which were positive for dengue IgM alone by the NIV MAC-ELISA, only 2 (25%) each were picked up by the other 2 tests. While out of 7 samples positive for IgM to all three flaviviruses IgM by the NIV MAC-ELISA, 5 (71%) were picked up by the other 2 tests. Of the 5 that were picked up by the PanBio tests, 3 had the highest absorbance values to WN by the NIV MAC-ELISA, indicating cross reactivity by PanBio tests. INTERPRETATION & CONCLUSION: The MAC-ELISA though a 3 day procedure, would be a valuable screening test for the detection of IgM to dengue in routine diagnostic laboratories because of its high sensitivity and specificity rates. The test uses specific viral antigens to detect IgM antibodies not only to dengue but also to JE and West Nile as a result of which IgM antibodies to all the 3 commonly encountered flaviviruses can be detected in a single run. It also has the advantage in that depending on the strength of the antibody units obtained to a specific flaviviral antigen, presumptive diagnosis as to which particular arboviral infection has occurred can be made in conjunction with clinical presentation.

Antibodies, Viral↗

Hepatic dysfunction in dengue patients with various severity.

This prospective study was designed to evaluate the correlation between biochemical changes in hepatic function and severity of dengue infection in pediatric patients. One hundred and four children with a clinically and serologically confirmed diagnosis of dengue infection were classified into the non-shock group, i.e. 20 cases of dengue fever and 27 cases of dengue hemorrhagic fever, and the shock group comprising 57 cases of dengue shock syndrome. Liver function tests were performed within the first three days after defervescence or shock. The study showed that levels of aspartate transaminase and alanine transaminase were significantly higher, whereas, globulin level was significantly lower among patients with more severe disease (p < 0.05). Levels of albumin, alkaline phosphatase, bilirubin and prothrombin time were not different among the groups. In conclusion, hepatic dysfunction in dengue patients is a common condition. Patients with more severe disease have significantly higher transaminase and lower globulin levels.

Adolescent↗

[Effect of dengue virus infection on the production of ET-1 and PGI2 by human vascular endothelial cells].

OBJECTIVE: To study the effect of dengue virus infection on the production of endothelin 1(ET-1) and prostacyclin 2(PGI2) by human umbilical cord vein endothelial cells (HUVECs). METHODS: HUVECs were infected by dengue-2 virus (DV-2), the culture supernatants were collected at 4, 24, 48, 72 and 96 hours postinfection, and the levels of ET-1 and PGI2 were measured by radio-immunoassay. RESULTS: The results showed that inhibition of production of ET-1 and PGI2 was induced by dengue virus infection in HUVECs. Marked inhibition of ET-1 and PGI2 production was observed as early as 4 h postinfection and the inhibitory effect continued until 96 h postinfection. Significant differences were shown between the ET-1 concentration of the virus-infected and non-infected cells. Nevertheless, the inhibitory effect of dengue virus infection on the production of PGI2 gradually decreased and the PGI2 concentration reverted to normal level at 96 h postinfection. No significant difference between the PGI2 concentration of the virus-infected and non-infected cells was seem. CONCLUSION: The present study suggests that dengue virus infection of vascular endothelial cells could affect their normal functions of secretion of vasoactive substances, resulting in increased vascular permeability and impairment of homostasis and blood coagulation. Therefore, functional impairment of vascular endothelial cells induced by dengue virus might be an important aspect in the pathogenesis of DHF/DSS.

Cells, Cultured↗

First documented outbreak of dengue in the Peruvian Amazon region.

This article describes a classical dengue outbreak caused by dengue serotypes 1 and 4 that occurred from March to July 1990 in the city of Iquitos and surrounding areas of Loreto Department in the Peruvian Amazon. Epidemiologic data indicate that more than 150,000 persons may have been affected in Iquitos alone. Another dengue outbreak occurred in Tarapoto, a city in the neighboring department of San Martín. Laboratory data indicate that the same dengue serotypes were involved in both outbreaks. No cases of dengue hemorrhagic fever/shock syndrome appear to have occurred. Prior to this outbreak, no indigenous dengue cases had been documented in Peru.

Dengue↗

[Prenatal and postnatal effects of dengue infection during pregnancy].

The risk of dengue virus infection during pregnancy has increased due to the current rash of frequent and severe dengue epidemics. The effects of dengue virus in the fetus and newborn children have been studied only superficially and with contradictory results. Therefore, a retrospective cohort study was conducted in Medellin, Colombia, to describe the fetal and postnatal effects of dengue virus infection acquired during pregnancy. Twenty-two babies born from mothers who suffered dengue during the epidemics of 1998 were compared with babies from non-infected mothers. In the exposed cohort, three premature births occurred, three children suffered from fetal anomalies and four children were born with low weight. In the non-exposed children, none of these problems were found. Psychomotor development was normal in both groups. Only the low weight subgroup was statistically significant (Fisher test, p = 0.045). These results suggested that the children from women with dengue during pregnancy present low weight, greater frequency of premature birth and increased fetal distress. A larger sample is necessary to confirm these results.

Cohort Studies↗

[Susceptibility of 15 collections of Aedes albopictus from Guizhou to dengue virus oral infection].

OBJECTIVE: To study the susceptibility of Aedes albopictus to dengue virus infection. METHODS: Aedes albopictus from 15 collections in Guizhou province were challenged orally with dengue virus 1-4 types, respectively. The total RNA from mosquitos were extracted. The viral NS1 gene fragment was amplified with reverse transcriptase polymerase chain reaction (RT-PCR). Dengue virus in mosquitoes was isolated with C6/36 cells. Then the viral antigen was detected by indirect immunofluorescence assay (IFA). Antigen and nucleic acid of dengue virus from 15 geographic strains of Aedes albopictus orally infected with dengue viruses (DEN-1, DEN-2, DEN-3 and DEN-4) were detected by IFA, RT-PCR and the virus was isolated with C6/36 cells, respectively. RESULTS: The rates of Aedes albopictus orally infected with DEN-1, DEN-2, DEN-3 and DEN-4 were 12/15, 12/15, 8/15 and 13/15, respectively. CONCLUSIONS: Different geographic strains of Aedes albopitus in Guizhou were susceptible to dengue viruses.

Aedes↗

Travel-associated dengue infections--United States, 2001-2004.

Dengue is a mosquito-transmitted, acute viral disease 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 in U.S. residents returning from travel to such areas. CDC maintains a laboratory-based passive surveillance system for travel-associated dengue among U.S. residents. The system relies on voluntary reports submitted to state health departments by clinicians; patient specimens are then forwarded to CDC for diagnostic testing. This report summarizes information about travel-associated dengue cases among U.S. residents during 2001-2004. The risk for dengue infection among travelers can be reduced by use of repellents and by avoiding exposure to mosquitoes.

Dengue↗

Economic impact of dengue fever/dengue hemorrhagic fever in Thailand at the family and population levels.

Dengue fever and dengue hemorrhagic fever constitute a substantial health burden on the population in Thailand. In this study, the impact of symptomatic dengue virus infection on the families of patients hospitalized at the Kamphaeng Phet Provincial Hospital with laboratory-confirmed dengue in 2001 was assessed, and the disability-adjusted life years (DALYs) lost for fatal and non-fatal cases of dengue were calculated using population level data for Thailand. When we accounted for the direct cost of hospitalization, indirect costs due to loss of productivity, and the average number of persons infected per family, we observed a financial loss of approximately US$61 per family, which is more than the average monthly income in Thailand. The DALYs were calculated using select results from a family level survey, and resulted in an estimated 427 DALYs/million population in 2001. This figure is of the same order of magnitude as the impact of several diseases currently given priority in southeast Asia, such as the tropical cluster (trypanosomiasis, Chagas disease, schistosomiasis, leishmaniasis, lymphatic filariasis, and onchocerciasis), malaria, meningitis, and hepatitis. These results indicate that dengue prevention, control, and research should be considered equally important as that of diseases currently given priority.

Adolescent↗

Dengue in Grenada.

OBJECTIVES: Dengue fever is endemic in the country of Grenada and is grossly underreported as a source of morbidity. The goal of this study was to assess the status of dengue fever in a representative community in Grenada. METHODS: Surveys were conducted in the Mont Tout/Grand Anse Valley area in the parish of St. George's from March to June 1996. The objectives of the survey were to: (1) to assess the knowledge, attitudes, and practices (KAP) of residents; (2) to determine the presence of larval and adult Aedes aegypti and their potential breeding sites; and (3) to identify the seroprevalence of specific immunoglobulin G (IgG) dengue antibodies in the local population. RESULTS: Out of the 102 respondents to the KAP survey, 100 of them (98%) reported never having had dengue fever. Of the 75 persons who agreed to have blood samples taken, 70 of them (93%) (95% confidence interval = 85.1%-97.8%) tested positive with the IgG enzyme-linked immunosorbent assay, indicating past exposure. In terms of water storage, 98 of 102 respondents (96%) stored fresh water in containers. The vector survey found 57 of the 102 households (56%) had Ae. aegypti larvae in water containers on their property, and 94 of 102 dwellings (92%) had adult Ae. aegypti mosquitoes indoors. CONCLUSIONS: Although many people were familiar with dengue fever and mosquitoes, the 1996 survey found that their knowledge of the important relationships among mosquitoes, human behavior, and disease transmission was incomplete. Since 1996, continued education efforts have been made in the public school system and with national public health campaigns, yet little effort has been specifically targeted towards our study community. These data suggest Grenada has a need for continued community education that addresses dengue fever transmission and Ae. aegypti reduction.

Dengue↗

[Evaluation of the World Health Organization clinical definition of dengue].

INTRODUCTION: The distinction between dengue and other acute febrile diseases is difficult when based solely on symptoms. OBJECTIVE: An attempt was made to evaluate usefulness of dengue diagnoses in an endemic area (Bucaramanga, Colombia), based on the definitions recommended by the World Health Organization. MATERIALS AND METHODS: In a cohort >12 years of age with indications of acute febrile illness, the sensitivity, the specificity and the predictive values were determined based on the WHO dengue definition. Two or more of the following symptoms were included: headache, retroorbital pain, myalgia, arthralgia, rash, hemorrhagic manifestations, or leucopenia. RESULTS: One hundred-one cases of dengue and 89 patients with acute febrile illness were enrolled in the study. The dengue cases were confirmed by serological or by virus presence. The WHO case definitions showed sensitivity, 99%; specificity, 1%; positive predictive value, 53%, and negative predictive value, 50%. CONCLUSION: This clinical definition demonstrated high sensitivity, but a low specificity. Therefore, the clinical definition was useful for screening, but it did not differentiate between dengue and other febrile diseases.

Adolescent↗

Spatial, environmental and entomological risk factors analysis on a rural dengue outbreak in Lundu District in Sarawak, Malaysia.

The objective of this study was to elucidate the association of various risk factors with dengue cases reported in Lundu district, Sarawak, by analyzing the interaction between environmental, entomological, socio-demographic factors. Besides conventional entomological, serological and house surveys, this study also used GIS technology to generate geographic and environmental data on Aedes albopictus and dengue transmission. Seven villages were chosen based on the high number of dengue cases reported. A total of 551 households were surveyed. An overall description of the socio-demographic background and basic facilities was presented together with entomological and geographical profiles. For serological and ovitrap studies, systematic random sampling was used. Serological tests indicated that 23.7% of the 215 samples had a history of dengue, either recent or previous infections. Two samples (0.9%) were confirmed by IgM ELISA and 49 samples (22.8%) had IgG responses. A total of 32,838 Aedes albopictus eggs were collected in 56 days of trapping. Cluster sampling was also done to determine whether any of the risk factors (entomological or geographical) were influenced by geographical location. These clusters were defined as border villages with East Kalimantan and roadside villages along Lundu/Biawas trunk road. The data collected were analyzed using SPSS version 10.01. Descriptive analysis using frequency, means, and median were used. To determine the association between variables and dengue cases reported, and to describe the differences between the two clusters of villages, two-sample t-test, and Pearson's Chi-Square were used. Accurate maps were produced with overlay and density function, which facilitates the map visualization and report generating phases. This study also highlights the use of differential Global Positioning System in mapping sites of 1m accuracy. Analysis of the data revealed there are significant differences in clusters of villages attributable to container density, house density, distance of the house from the main road, and number of Ae. albopictus eggs from ovitraps set indoor, outdoor and in dumping sites (Person's Chi-Square = 6.111, df = 1, p < 0.01). Further analysis using t-test showed that house density, container density, indoor mosquitoes egg count, outdoor mosquitoes egg count, and dumping sites mosquitoes egg count were higher at the roadside villages compared to border villages. A number of potential risk factors including those generated from GIS were investigated. None of the factors investigated in this study were associated with the dengue cases reported.

Aedes↗