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PubMed1989

[Studies on the susceptibility among geographic strains of Aedes albopictus in China to infection with dengue viruses].

The comparative susceptibility to dengue serotype 1, 2 and 4 viruses infection of 9 geographic strains of Azdes albopictus was studied by means of experimental feeding the mosquitoes on pledgets soaked with virus-erythrocyte suspension and intrathoracic inoculation with dengue viruses. Variation in susceptibility for both dengue serotypes 1 and 2 was found among the geographic strains by feeding, but no significant difference among those by intrathoracic inoculation. It was evident that a "gut barrier" was involved. Thresholds of oral infection were not the same for dengue serotypes 1, 2 and 4. In terms of infection rate, Haikou strain was more susceptible to all three serotypes of viruses; Beijing and Chengdu strains were more susceptible to serotypes 1 and 2, respectively. All the geographic strains were more susceptible to dengue serotype 2 comparing with other two serotypes. The mosquito head squash method for demonstrating dengue virus antigen by indirect fluorescent antibody technique was modified by mosquito brain tissue smear. This would be more accurate in detecting the dengue virus antigen in the brain tissue.

Aedes↗
PubMed1981

Viraemia in patients with naturally acquired dengue infection.

The magnitude and duration of dengue viraemia were studied in 153 patients with naturally acquired dengue infection in Jakarta, Indonesia. The duration of viraemia ranged from 2 to 12 days, but most patients had detectable circulating virus for 4-5 days. Accurate measurement of peak virus titres was not possible for many patients because of late admission to the hospital. Composite pictures of viraemia for each serotype, however, showed that many patients infected with dengue 1, 2, or 3 had circulating virus titres ranging from barely detectable to over 10(8) MID(50) per ml for 3-5 days. Virus titres in patients infected with dengue 4 were about 100-fold lower. Dengue haemagglutination-inhibition antibody titres of 80 or less had little effect on viraemia, but antibody titres of 160 or greater were associated with a decrease in virus isolation rate and in virus titre. The duration and magnitude of viraemia did not vary significantly with the severity of the disease and was only slightly higher in patients classified as primary dengue infections than in those classified as secondary infections. Measurement of viraemia in fatal dengue haemorrhagic fever (DHF) cases showed that these patients had significant quantities of circulating virus at the time of death.

Dengue↗
PubMed1993

[Dengue epidemic in New Caledonia (1989). Environmental factors and prevention].

An extensive dengue epidemic was reported in New Caledonia en 1989. Environmental factors (temperature and rainfalls) directly controlled the mosquitos population at the end of 1988. The introduction of a new dengue virus, transmitted by Aedes aegypti, was responsible for an epidemic that occurred in January-April 1989 and lasted until July 1989. The estimated number of cases was 25,000 and the attack rate was close to 120 per thousand inhabitants for a six month-period. The epidemic involved mainly the adult population in 84% of cases and 6-8% of patients was admitted in hospital with thrombopenia, leucopenia, minor haemorrhages in 2/3 of cases and 12 patients died with severe hemorrhagic disease or shock syndrome; initial serological results from suspected cases were positive against dengue by haemaglutination inhibition. Two dengue viruses were involved (dengue 1 and dengue 3) but dengue 3 was by far the most common. Ultra-low volume aerosols of diluted insecticide (decamethrine K'Othrine, Roussel) from road vehicles and aircraft was used from February to May to kill the adult mosquitoes (adulticiding). The efficacy dependent on the interaction of the insecticide and the flying mosquitoes is relative and debated but played probably a major role on the transmission, though the reduction of breeding sites was primarily uncovered. Since the epidemic, only sporadic cases were observed in 1991 and 1992.

Animals↗
PubMed1997

Dengue virus infection of human T lymphocytes.

We have previously reported (Kurane et al., Arch. Virol. 110, 91-101, 1990) that human T cell leukemia and lymphoma cell lines could be infected with dengue virus. In the present study we examined whether human T lymphocytes which are not leukemia or lymphoma cells can be infected with dengue virus. Dengue virus-specific human CD4+ T cell clones, JK44 and JK49, and CD8+ T cell clones, CB2.8 and CB6.17, were infected with dengue-2 virus. Dengue virus antigen-positive cells were detected in each of the four T cell lines by the immunofluorescence staining 20-60 hrs post infection (p.i). Infectious dengue virus was detected in the culture fluids 40 hrs p.i. These results demonstrate that activated CD4+ and CD8+ human T lymphocytes can be infected with dengue-2 virus.

Aedes↗
PubMed1998

[Dengue: a re-emerging disease. A clinical and epidemiological study in 57 Spanish travelers].

Dengue infection is nowadays considered a re-emergent disease. It has a worldwide tropical and subtropical distribution. The dengue virus in a member of the flavivirus family composed by 4 different serotypes. The virus is transmitted by mosquitos of the Aedes genus. With the increment of travels to the endemic areas, dengue is now observed frequently in our country. We analyzed 57 patients, 30 with imported dengue (ID) and 27 with dengue fever suffered during the trip (DDT). This series is compared with other published ones and a review of the subject is presented. Patients with ID followed a protocol as a febril syndrome returning from the tropics. Dengue was diagnosed through a compatible clinico-epidemiological history, the absence of other ferbil illness and positivity of specific serology. All patients had travelled to endemic areas (Central America 28 cases, Indian subcontinent 15, South-East Asia 10, South America 2, West Africa one, and Pacific one). The following were the most important clinical characteristics: fever and asthenia (100%), headache (98%), mialgia (84%), arthralgia (72%), morbilliform rash (61%) and retroocular pain (65%). For ID cases, the most helpful analitical results were: leucopenia (70%), reactive lymphocytes in peripheral blood smear (70%), thrombocytopenia (70%), and increased hepatic enzymes ALAT (53%), ASAT (63%) and LDH (100% in the 7 patients tested for this enzyme). Dengue must be included in differential diagnosis of fever in patients coming back to travels to tropical areas.

Animals↗
PubMedDate not supplied

Dengue virus infection among children with undifferentiated fever in Karachi.

Sera were collected from a total of 122 children, comprising 117 cases with undifferentiated fever and 5 cases with dengue hemorrhagic fever (DHF), during June to September 1994 in Karachi, Pakistan. Sera were tested by the IgM-capture ELISA using dengue type 1 (D1), dengue type 2 (D2), West Nile (WN), and Japanese encephalitis (JE) viral antigens. Among 92 single sera from undifferentiated fever cases, IgM antibodies were detected in 5 cases by D1, 8 cases by D2, and 5 cases by WN antigens, respectively. Corresponding number of positives among 25 paired sera from undifferentiated fever cases were 3 by D1, 6 by D2, and 1 by WN antigen. Four out of 5 DHF cases possessed anti-D1 as well as anti-D2 IgM antibodies. Only a single DHF case was positive for anti-WN IgM antibodies. Anti-JE IgM antibodies were not detected in any of the tested serum specimens. Clinical manifestations of undifferentiated fever patients were generally non specific, but the percentage of children with anemia, hepatomegaly and splenomegaly was higher in patients possessing anti-dengue IgM antibodies than those without. Among the groups with anti-dengue IgM antibodies, those possessing only anti-D2 but not anti-D1 IgM antibodies showed higher percentages with cough, edema, and splenomegaly. The results indicated that up to 26% of the undifferentiated fever cases were caused by dengue virus infection in Karachi, Pakistan.

Antibodies, Viral↗
PubMed2006

Symptoms and risk factors of ocular complications following dengue infection.

BACKGROUND: Dengue infection can result in severe ocular complications. We prospectively studied the range of ocular symptoms in a cohort of patients with dengue infection. METHODS: We included adult patients with serologically confirmed dengue infection who received clinical care at the National University Hospital, Singapore. They were assessed for demographic characteristics, ocular symptoms, laboratory parameters and dengue severity. Patients with two or more ocular symptoms were referred to an ophthalmologist and underwent full ophthalmologic examination that included visual acuity, slit-lamp examination and indirect fundoscopic examination. Descriptive and logistic regression analyses were performed and statistical significance was set at p<0.05. RESULTS: One hundred and fifty-six patients, aged (S.D.) 33.94 (12.7) years, consisting of 89 (57.1%) males and 67 (42.9%) females, participated in this study. They reported ocular symptoms, such as eye strain (30%), retro-ocular pain (20%), blurring of vision (10%), double vision (3%), foreign body sensation (3%), eye flashes (2%) and floaters (1%). Multivariate analysis identified white cell count (odds ratio, OR 0.531; 95% CI 0.292, 0.963) and serum albumin (OR 0.758; 95% confidence intervals, CI 0.618, 0.928) as significant predictors of clinically significant ocular symptoms. The triad of symptoms (eye flashes, floaters and blurring of vision) was highly predictive for the development of retinal hemorrhages (positive predictive value 100%). CONCLUSIONS: Dengue virus results in a spectrum of ocular manifestations, ranging from non-specific symptoms to severe retinal hemorrhages. Further studies are needed to validate the triad of ocular symptoms as a screening tool for severe ocular complications following dengue infection.

Adult↗
PubMed2002

HLA-A and -B allele associations with secondary dengue virus infections correlate with disease severity and the infecting viral serotype in ethnic Thais.

Little is known of the role of classical HLA-A and -B class I alleles in determining resistance, susceptibility, or the severity of acute viral infections. Appropriate paradigms for immunogenetic studies of acute viral infections are dengue fever (DF) and dengue hemorrhagic fever (DHF). Both primary and secondary infections with dengue virus (DEN) serotypes 1, 2, 3 or 4, can result in either clinically less severe DF or the more severe DHF. In secondary exposures, a memory response is induced in immunologically primed individuals, which can both clear the infecting dengue virus and contribute to its pathology. In a case-control study of 263 ethnic Thai patients infected with either DEN-1, -2, -3 or -4, we detected HLA class I associations with secondary infections, but not in immunologically naive patients with primary infections. HLA-A*0203 was associated with the less severe DF, regardless of the secondary infecting virus serotype. By contrast, HLA-A*0207 was associated with susceptibility to the more severe DHF in patients with secondary DEN-1 and DEN-2 infections only. Conversely, HLA-B*51 was associated with the development of DHF in patients with secondary infections, and HLA-B*52 was associated with DF in patients with secondary DEN-1 and DEN-2 infections. Moreover, HLA-B44, B62, B76 and B77 also appeared to be protective against developing clinical disease after secondary dengue virus infection. These results confirm that classical HLA class I alleles are associated with the clinical outcome of exposure to dengue virus, in previously exposed and immunologically primed individuals.

Adolescent↗
PubMed2015

Dengue virus infection elicits highly polarized CX3CR1+ cytotoxic CD4+ T cells associated with protective immunity.

Dengue virus (DENV) is a rapidly spreading pathogen with unusual pathogenesis, and correlates of protection from severe dengue disease and vaccine efficacy have not yet been established. Although DENV-specific CD8(+) T-cell responses have been extensively studied, the breadth and specificity of CD4(+) T-cell responses remains to be defined. Here we define HLA-restricted CD4(+) T-cell epitopes resulting from natural infection with dengue virus in a hyperepidemic setting. Ex vivo flow-cytometric analysis of DENV-specific CD4(+) T cells revealed that the virus-specific cells were highly polarized, with a strong bias toward a CX3CR1(+) Eomesodermin(+) perforin(+) granzyme B(+) CD45RA(+) CD4 CTL phenotype. Importantly, these cells correlated with a protective HLA DR allele, and we demonstrate that these cells have direct ex vivo DENV-specific cytolytic activity. We speculate that cytotoxic dengue-specific CD4(+) T cells may play a role in the control of dengue infection in vivo, and this immune correlate may be a key target for dengue virus vaccine development.

Adult↗
PubMed1998

Dengue vaccine design: issues and challenges.

Dengue virus infection is now a global problem affecting tens of millions of people. The spread of the four dengue virus serotypes had led to increased incidence of dengue haemorrhagic fever (DHF) reported and with 2.5 billion people at risk, efforts towards the development of safe and effective vaccines against dengue must be accelerated. This chapter reviews some of the important lessons of pathogenesis which may be learnt from classical studies in the field and place these in the context of current knowledge about the molecular biology of the virus. The issues which have to be addressed in designing a safe vaccine against dengue are raised and the problems of designing subunit as well as whole virus vaccines are pointed out, particularly with regard to the phenomenon of antibody dependent enhancement and, more generally, the problem of immune potentiation of disease. More efforts must be made to understand the basis of pathogenesis in DHF and in finding out what nature has to teach about protection against and recovery from dengue virus infection.

DNA, Viral↗
PubMed2000

Comparison of rapid centrifugation assay with conventional tissue culture method for isolation of dengue 2 virus in C6/36-HT cells.

A rapid centrifugation assay was compared with conventional tube cell culture for dengue virus isolation in both sera and autopsy samples from dengue and dengue hemorrhagic fever/dengue shock syndrome fatal cases. The rapid centrifugation assay allowed isolation of virus from 16.6% more samples than the conventional method, and it shortened the time for dengue virus detection. Finally, it allowed the isolation of dengue 2 virus in 42.8% of tissue samples from five fatal cases. Our results suggest that the rapid centrifugation assay may be useful for detection of dengue virus in clinical specimens.

Aedes↗
PubMed2006

Virus-induced decline in soluble vascular endothelial growth receptor 2 is associated with plasma leakage in dengue hemorrhagic Fever.

Some individuals infected with dengue virus develop dengue hemorrhagic fever (DHF), a viral hemorrhagic disease characterized by a transient period of localized plasma leakage. To determine the importance of vascular endothelial growth factor A (VEGF-A) in this syndrome, we compared plasma levels of VEGF-A and the soluble forms of its receptors in patients with DHF to patients with dengue fever (DF), a milder form of dengue virus infection without plasma leakage. We observed a rise in the plasma levels of free, but not total VEGF-A in DHF patients at the time of plasma leakage. This was associated with a decline in the soluble form of VEGF receptor 2 (VEGFR2) and VEGF-soluble VEGFR2 complexes, but not the soluble form of VEGFR1. The severity of plasma leakage in patients inversely correlated with plasma levels of soluble VEGFR2. In vitro, dengue virus suppressed soluble VEGFR2 production by endothelial cells but up-regulated surface VEGFR2 expression and promoted response to VEGF stimulation. In vivo, plasma viral load correlated with the degree of decline in plasma soluble VEGFR2. These results suggest that VEGF regulates vascular permeability and its activity is controlled by binding to soluble VEGFR2. Dengue virus-induced changes in surface and soluble VEGFR2 expression may be an important mechanism of plasma leakage in DHF.

Capillary Permeability↗
PubMed2000

Dengue infection presenting with central nervous system manifestation.

The objective of this study was to investigate the possibility of dengue virus infection causing an abnormal neurologic presentation. Between 1996 and 1998, all pediatric patients with clinical manifestations of encephalitis-like illness who were admitted to the Department of Pediatrics, Siriraj Hospital were prospectively studied for any evidence of dengue virus infection. The diagnosis of dengue virus infection was based on mosquito viral isolation and serologic and polymerase chain reaction (PCR) evidence. Of 44 patients with the preliminary diagnosis of acute viral encephalitis, 8 were diagnosed with dengue infection. All of these 8 patients were diagnosed by serology. In addition to the serologic diagnosis, four also had positive PCR, one had positive viral isolation, and one had both positive PCR and viral isolation. Only two patients were diagnosed by serologic evidence alone. All except one had clinical courses and laboratory findings compatible with typical dengue infection. All had obvious encephalitic clinical manifestations with normal cerebrospinal fluid findings except one patient, who had mildly increased cerebrospinal fluid protein. All of these patients recovered completely and had benign clinical courses except one patient, who developed leakage symptoms. None had liver failure. Dengue virus can cause acute encephalopathy with fever. It can masquerade as other types of acute viral encephalitis. However, its clinical course and prognosis are usually favorable.

Acute Disease↗
PubMed2004

Aminotransferase changes and acute hepatitis in patients with dengue fever: analysis of 1,585 cases.

INTRODUCTION: Type 3 dengue virus caused an extensive epidemic in the state of Rio de Janeiro in summer 2002. In some of the patients, it was found in an atypical form with increased aminotransferase levels and acute hepatitis. MATERIAL AND METHODS: An analysis was made of 1,585 serologically confirmed dengue cases at the Dengue Reference Center in Campos dos Goytacazes, Rio de Janeiro state. The grade of hepatic aggression was established according to the alterations in the aminotransferase levels: grade A -- normal levels of aminotransferase; grade B -- elevated aminotransferase, with increased levels of at least one of the enzymes; grade C -- elevated aminotransferase, with the levels of at least one of the enzymes increased to more than three times the reference values; grade D -- acute hepatitis, with aminotransferase levels increased to at least 10 times their normal values. RESULTS: Among the 1,585 serologically confirmed dengue cases, 44.5% presented alterations in the aminotransferase levels (grade B), 16.9% presented grade C liver involvement and 3.8% of the patients had progressed to acute hepatitis (grade D). The average values for the rise in aspartate aminotransferase and alanine aminotransferase were 93.3 U/L and 86.0 U/L. The greatest alterations were observed among females (p<0.001), cases of dengue hemorrhagic fever (p<0.001), and cases with sequential infections (p=0.001). CONCLUSIONS: Liver damage with elevation of aminotransferases and reactive hepatitis was a common complication of dengue virus infection in these patients.

Acute Disease↗
PubMed2006

Serodiagnosis of dengue virus infection in patients presenting to a tertiary care hospital.

Dengue is an acute infectious disease of viral etiology. It is probably one of the most important arthropod borne viral disease in terms of human morbidity and mortality. The spectrum of disease ranges from self-limited dengue fever to more severe forms of dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Laboratory diagnosis of dengue virus infection mainly depends on detection of virus specific antibodies. The aim of the study was to correlate the serological results with clinical presentation in patients with a diagnosis of dengue. Eleven out of 15 (73.3%) patients with DHF and DSS had secondary antibody response and mortality was 100% in these patients.

Academic Medical Centers↗
PubMed1998

Two contiguous outbreaks of dengue type 2 in north Queensland.

OBJECTIVES: To investigate two outbreaks of dengue type 2 in north Queensland, one in the Torres Strait beginning in late 1996, the other in a Cairns suburb in early 1997. DESIGN: Epidemiological investigation of all laboratory-confirmed cases of dengue, entomological investigation of the local environment, and laboratory analysis of the isolated dengue viruses. MAIN OUTCOME MEASURES: Numbers of confirmed and of locally acquired cases; virus serotype; comparison of nucleotide sequences between viruses isolated from the two outbreaks; and Breteau Index (BI = number of containers with larvae of the mosquito vector Aedes aegypti found per 100 houses investigated) on the affected islands and in the Cairns suburb. RESULTS: There were 201 confirmed cases of dengue in the Torres Strait outbreak, which lasted nearly seven months, and seven confirmed cases in the Cairns outbreak, which lasted about nearly 11 weeks. Most (190) were confirmed as dengue type 2. Nucleotide sequencing of viruses isolated from the two outbreaks showed they were identical. Ae. aegypti breeding sites were very common on the five Torres Strait islands surveyed (BIs, 73-219--high risk), but less so in the Cairns suburb (BI, 23). The most common breeding sites were water storage reservoirs, particularly rainwater tanks, on the outer Torres Strait islands, discarded containers (such as plastic containers, buckets and tyres) on Thursday Island, and garden items (such as flowerpot bases and jars) in Cairns. CONCLUSIONS: The virus responsible for the Cairns outbreak was most probably introduced from the Torres Strait, whereas the virus responsible for the Torres Strait outbreak was imported from Papua New Guinea. Preventive strategies tailored to specific locations are needed to reduce breeding of Ae. aegypti in north Queensland, and the consequent risk of future outbreaks of dengue.

Adolescent↗
PubMed2003

[Laboratory diagnosis of dengue virus infections in Aragua State, Venezuela: October 1997-December 1998].

The efficacy of a proactive dengue surveillance system to predict epidemics depends on the laboratory diagnostic capacity for an early detection of virus circulation. This study shows the results of the dengue virologic and serologic surveillance accomplished in Aragua State (Venezuela) from October 1997 to December 1998. Five hundred and forty seven sera from suspected dengue patients were tested using the techniques of Virus Isolation and Immunofluorescence Serotyping (VIIS), Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR), Anti-dengue IgM Capture Enzyme Immunoassay (MAC-ELISA) and Haemagglutination Inhibition test (HI). Of the tested sera, 97.4% resulted positive to at least one technique; of these, 60.4% were classified as confirmed cases (virologically positives) and 39.6% as probable cases (virologically negatives/serologically positives). Though the majority of positive cases occurred during the 1997 and 1998 epidemic periods, the gradual increase of the seropositive rates between both periods suggested the incoming 1998 outbreak. Den-1 (51.2%), Den-2 (37.9%) and Den-4 (10.6%) infected patients were detected as well as one dual infection of Den-2 and Den-4 (0.3%). Dengue hyperendemicity (co-circulation of Den-1, Den-2 and Den-4) in Aragua State was confirmed together with the detection of few cases (6.5%) of Dengue Hemorrhagic Fever/Dengue Shock Syndrome cases (HF/DSS); 38.1% of these cases occurred in patients with secondary infections. The high percentage (85.7%) of DHF/DSS cases infected by Den-2 virus supports the reported virulence of this serotype.

Dengue↗
PubMed2004

Clinical diagnosis and assessment of severity of confirmed dengue infections in Vietnamese children: is the world health organization classification system helpful?

Classification of dengue using the current World Health Organization (WHO) system is not straightforward. In a large prospective study of pediatric dengue, no clinical or basic laboratory parameters clearly differentiated between children with and without dengue, although petechiae and hepatomegaly were independently associated with the diagnosis. Among the 712 dengue-infected children there was considerable overlap in the major clinical features. Mucosal bleeding was observed with equal frequency in those with dengue fever and dengue hemorrhagic fever (DHF), and petechiae, thrombocytopenia, and the tourniquet test differentiated poorly between the two diagnostic categories. Fifty-seven (18%) of 310 with shock did not fulfill all four criteria considered necessary for a diagnosis of DHF by the WHO, but use of the WHO provisional classification scheme resulted in considerable over-inflation of the DHF figures. If two separate entities truly exist rather than a continuous spectrum of disease, it is essential that some measure of capillary leak is included in any classification system, with less emphasis on bleeding and a specific platelet count.

Adolescent↗