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PubMed1999

[Dengue]

OBJECTIVE: To review the literature about epidemiological, clinical and preventive aspects of hemorrhagic dengue fever in children, and to provide Brazilian pediatricians with an update on dengue METHODS: We reviewed MEDLINE and classic texts.RESULTS: Dengue is an arbovirus disease, transmitted by Aedes aegypti, a mosquito that feeds indoors and is disseminated in Brazil. Its clinical presentation ranges from asymptomatic forms to acute disease with fever, myalgia, headache and rash. Evolution with hemorrhage, hemoconcentration, decreased platelets and shock is characteristic of dengue shock syndrome. Mortality rate is high, chiefly in children, if not treated earlier. There is no specific antiviral treatment, but a polyvalent vaccine is presently being evaluated.CONCLUSION: Among the prevalent acute infectious diseases in our setting, dengue is one of the most frequent, and may be highly lethal if associated with shock. Vector control is still the most effective prophylactic measure.

Journal Article↗

PubMed2026

Frequent introductions and climate suitability drive increasing dengue risk in Florida.

In recent years, detection of local dengue cases in Florida have increased in both frequency and geographical extent. From 2022 to 2024, consecutive outbreaks in Miami-Dade County were mainly caused by a single lineage of dengue virus (DENV) serotype 3, prompting questions about changing epidemiology and a transition towards endemicity. In this study, we used mathematical modeling and genomic epidemiology to reveal the spatiotemporal dynamics and drivers of local dengue cases in Florida. We found that annual clusters and outbreaks were caused by frequent short-lived DENV introductions, primarily from the Caribbean, and did not find evidence for local trans-seasonal DENV lineage persistence. Further, we show that the climate-driven increases in local suitability for Aedes aegypti transmission and travel-associated cases were the greatest risk factors for outbreaks in Miami-Dade and the geographic expansion of dengue in Florida. Overall, while we do not yet find evidence for endemicity, we demonstrate how climatic trends are enhancing the local public health risk caused by dengue in Florida.

Journal Article↗

PubMed1999

Sequential production of cytokines by dengue virus-infected human peripheral blood leukocyte cultures.

The study was undertaken to elucidate the sequence of appearance of T helper (Th)1- and Th2-type cytokines in human peripheral blood leucocyte cultures infected in vitro with dengue type 2 virus. Commercial sandwich enzyme-linked immunosorbent assay kits were used to assay the levels of tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin (IL)-2, IL-4, IL-5, IL-6, and IL-10 in culture supernatants. Culture supernatants were also screened for the cytotoxic factor and the dengue virus titres determined. The cytokines that appeared in the culture supernatants on the first day post-infection (p.i.) were cytotoxic factor, TNF-alpha, IL-2, and IL-6; their levels were highest on the second day p.i. IFN-gamma appeared on the second day with a peak on the third day p.i. The levels of these cytokines declined quickly, except for human cytotoxic factor (hCF) and IL-2. The cytokines that appeared later were IL-10 and IL-5 on the fourth day and IL-4 on the sixth day p.i. Dengue virus replicated in the peripheral blood leucocyte (PBL) cultures and was present throughout the course of the study. The findings of the present study show that dengue virus induced a predominant Th1-type cytokine response during the first 3 days of infection of PBL cultures that was replaced by a Th2-type response later.

Animals↗

PubMed2003

Tissue plasminogen activator induced by dengue virus infection of human endothelial cells.

Dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) are severe complications of dengue virus (DV) infection. However, the pathogenesis of hemorrhage induced by dengue virus infection is poorly understood. Since endothelial cells play a pivotal role in the regulation of hemostasis, we studied the effect of DV infection on the production of tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) in vitro using both primary isolated endothelial cells, human umbilical cord veins cells, and a human microvascular endothelial cell line. DV infection significantly induced the secretion of tPA but not PAI-1 of human endothelial cells. In addition, tPA mRNA of endothelial cells was induced by DV as demonstrated by RT-PCR. Antibody against IL-6 but not control antibody inhibited DV-induced tPA production of endothelial cells. Furthermore, a good correlation between sera levels of IL-6 and tPA was found in DHF but not DF patients. These results suggest that IL-6 can regulate DV-induced tPA production of endothelial cells, which may play important roles in the pathogenic development of DHF/DSS.

Adolescent↗

PubMed1990

Study of anti-dengue NS1 antibody by western blot.

The presence of anti-nonstructural protein (NS1) antibody in natural dengue infections has been suspected to be associated with development of dengue haemorrhagic fever (DHF). The Western blot technique was used to study the dynamics of the immune response to NS1 and to determine the frequency of anti-NS1 antibody among confirmed dengue patients in Indonesia, where DHF is common, and in Puerto Rico, where DHF is less frequently observed. Anti-NS1 antibody was rarely found in those with primary infections in either group. The antibody occurred at a significantly higher frequency in acute-phase serum samples from secondary infections in Indonesia than in those from Puerto Rico. No difference was observed, however, in Indonesian patients with secondary infection who had dengue fever or DHF.

Antibodies, Viral↗

PubMed2006

SYBR green and TaqMan real-time PCR assays are equivalent for the diagnosis of dengue virus type 3 infections.

Dengue is the most important arthropod-borne viral disease in the world. A rapid diagnostic test for dengue is warranted, and real-time polymerase chain reaction may improve diagnosis. TaqMan and Sybr Green systems were evaluated for the diagnosis of dengue virus type 3 (DENV-3) infections. Out of 77 patients with clinical suspicion of dengue infection, specific IgM antibodies were detected in 40 patients. DENV-3 was detected and quantitated in 17 IgM-positive samples by both systems. These assays were shown to be rapid, and specific for detection of DENV-3, and that for diagnostic purposes, there is no difference between these two assays.

Dengue↗

PubMed2004

Predictors of spontaneous bleeding in Dengue.

OBJECTIVE: To identify the predictive factors for spontaneous bleeding manifestations in Dengue illness in infants and children. METHODS: 60 cases of Dengue viral infection with spontaneous skin and or mucosal bleed were compared with 72 cases without spontaneous bleed. The protean bleeding manifestations in dengue infection were recorded. Various clinical and laboratory parameters were analyzed using univariate and logistic regression analysis. RESULTS AND CONCLUSION: Prothombin time was abnormal only in cases with spontancous bleed. A combination of (a) biphasic pattern of fever, (b) hemoconcentration, (c) platelet count less than 50,000/mm3 and (d) elevated ALT had a sensitivity of 79.2%, specificity of 64.7% with a positive predictive value of 70% and a negative predictive value of 75% in predicting spontaneous bleeding in dengue.

Age Distribution↗

PubMed2006

[Hemorrhagic dengue fever after trip to Malaysia].

A 39-year-old patient developed a disseminated rash with scattered petechiae, fever, malaise and arthralgia after a trip to Malaysia. The patient displayed increasing dengue IgG titers and borderline dengue IgM titers. Dengue fever with a hemorrhagic course is a rare condition in adult patients. Patients who have previously had dengue fever and retained non-neutralizing heterotypic antibodies are more likely to develop this complication via the phenomenon of antibody-dependent enhancement.

Adult↗

PubMed1997

Competitive exclusion in a vector-host model for the dengue fever.

We study a system of differential equations that models the population dynamics of an SIR vector transmitted disease with two pathogen strains. This model arose from our study of the population dynamics of dengue fever. The dengue virus presents four serotypes each induces host immunity but only certain degree of cross-immunity to heterologous serotypes. Our model has been constructed to study both the epidemiological trends of the disease and conditions that permit coexistence in competing strains. Dengue is in the Americas an epidemic disease and our model reproduces this kind of dynamics. We consider two viral strains and temporary cross-immunity. Our analysis shows the existence of an unstable endemic state ('saddle' point) that produces a long transient behavior where both dengue serotypes cocirculate. Conditions for asymptotic stability of equilibria are discussed supported by numerical simulations. We argue that the existence of competitive exclusion in this system is product of the interplay between the host superinfection process and frequency-dependent (vector to host) contact rates.

Aedes↗

PubMed1983

Dengue haemorrhagic fever--case report.

A 29-year-old Dutch tourist of the Caucasian race had to break her return journey from Indonesia as she developed dengue haemorrhagic fever. She appeared to have been infected on Bali. Serological investigation revealed very high antibody titres against dengue virus types 1 and 3 and a moderately high titre against type 4 virus in the serum sample collected two weeks after onset of disease. In the sample taken 14 weeks after onset only more normalized antibody titres against type 1 and type 3 remained detectable. Although during earlier trips to the tropics she never showed signs of dengue fever, the timing of her first infection remains uncertain. The influence of age, race and double infections is discussed with relation to the cause of dengue haemorrhagic fever.

Adult↗

PubMedDate not supplied

Detection of dengue virus from mosquito cell cultures inoculated with human serum in the presence of actinomycin D.

We report the use of cultures of mosquito cells (TRA-284) to detect dengue virus in serum from cases of dengue fever in the state of Puebla, México. Using the conventional procedure 56 of 171 samples (32.7%) were positive. The negative sera (67.3%) were passaged 'blind' in mosquito cell cultures but no virus was detected. However, when these sera were incubated in the presence of actinomycin D (an inhibitor of deoxyribonucleic acid transcription) 20 of the 115 samples (17.4%) became positive. This procedure increased the virus detection rate from 32.7% to 44.4%. Serotypes 1 and 4 were identified for the first time in the state of Puebla, where the transmission of dengue virus is increasing. The addition of actinomycin D to mosquito cell cultures may improve the detection of dengue virus and could be a useful tool for virological surveillance in endemic countries.

Animals↗

PubMed1991

Dengue virus premembrane and membrane proteins elicit a protective immune response.

We have constructed recombinant vaccinia viruses that express the premembrane (pre-M), membrane (M), or the cleaved, residual portion of pre-M (non-M) proteins of dengue 4 virus, or the pre-M, non-M, or envelope (E) proteins of dengue 2 virus, to evaluate their ability to induce protective immunity in mice. Cells infected with these recombinants make proteins of expected size. Mice immunized with recombinants expressing dengue 4 pre-M or M were protected against subsequent dengue 4 encephalitis challenge, but non-M was not protective. However, a recombinant that expressed both pre-M and E as a polyprotein gave solid protection, while the simultaneous administration of the two recombinants expressing pre-M and E gave a significant level of protection. Pre-M and M function as antigens eliciting a protective immune response, and the combination of pre-M plus E is more protective than E alone.

Animals↗

PubMed1987

Neurovirulence detection of dengue virus using rhesus and cynomolgus monkeys.

The results of a comparative study of neurovirulence of dengue type 1 virus in two species of Old World monkeys, viz. rhesus monkeys (Macaca mulatta) and cynomolgus monkeys (Macaca fascicularis) are reported. In the present study, parental dengue type 1 (16007) and its vaccine viruses were tested by intrathalamic, intramuscular and intraspinal injections in these two species of monkey. Both species of monkeys inoculated with parental dengue type 1 virus developed neurovirulence-type lesions which were graded as minimal (V-1) and occasionally mild (V-2, in cynomolgus monkeys) in severity. The antibody response to either parental or vaccine virus was slightly less in rhesus monkeys than in cynomolgus inoculated with these strains. This comparative study possibly establishes the cynomolgus monkey as a suitable test model to replace the rhesus monkey for neurovirulence testing of dengue-1 vaccine intended for use in humans.

Animals↗

PubMed1988

Development of a dot enzyme immunoassay for dengue 3: a sensitive method for the detection of antidengue antibodies.

Partially purified DEN3 virus was used as antigen in a sensitive dot enzyme immunoassay (DEIA) for the detection of antibodies to flavivirus antigens. We describe here the method used to prepare and optimise the antigen-bearing nitrocellulose membranes and present the results obtained from screening 20 acute phase sera from patients shown to have had recent dengue infections by the haemagglutination inhibition (HI) test. Sixteen pairs of acute and convalescent sera from dengue-negative patients had no detectable antibody to dengue virus by HI. These were shown to have no antibody detectable by DEIA. Sera positive for dengue antibodies by HI had DEIA titers ranging from 10 to several thousand times greater than the titers detected by HI.

Antibodies, Viral↗

PubMed1994

A PCR-restriction enzyme technique for determining dengue virus subgroups within serotypes.

The polymerase chain reaction (PCR) and restriction enzyme analysis were used to develop a rapid and simple procedure for identifying geographic subgroups of dengue virus within serotypes for epidemiologic investigations. The entire structural protein region of dengue viruses was amplified and the products were digested with the endonucleases AluI or DdeI. By comparing the restriction fragment length polymorphisms (RFLPs), we recognized dengue-2 and dengue-3 subgroups that corresponded to those previously determined by oligonucleotide fingerprinting or genomic sequencing. This procedure can be performed in 2 days without the use of radioisotopes, and results can be interpreted without computer analysis. For those analyses which require only subgroup affiliations, this is a useful tool for rapidly screening multiple virus isolates.

Aedes↗

PubMed2005

Dengue virus infections: comparison of methods for diagnosing the acute disease.

BACKGROUND: The control of dengue depends solely on the control of the insect vector and efficient diagnosis of human cases as no vaccines or specific treatments are currently available. Existing diagnostic methods for suspected clinical cases are complicated by the short duration of viraemia and by serological cross-reactivity with epitopes from other flaviviruses. OBJECTIVES: To evaluate PCR-based tests (nested reverse transcription (RT)-PCR and real-time RT-PCR) for the detection and serotyping of dengue virus and compare the results with those obtained with a widely used immunological test (IgM antibody capture ELISA-MAC-ELISA). RESULTS AND CONCLUSIONS: The PCR-based methods were more effective in the first few days of infection, whereas the MAC-ELISA became more sensitive 5 or 6 days after disease onset. These results suggest that the best method for dengue diagnosis is a combination of PCR-based and immunological tests. Real-time RT-PCR was more sensitive than the nested RT-PCR approach. Furthermore, it was rapid, reproducible and highly specific, making it a potential method for the diagnosis of dengue fever.

Acute Disease↗

PubMed2006

Severe, persisting, steroid-responsive Dengue myositis.

OBJECTIVES: Short-term, general muscle affection is frequent in Dengue infection, but severe, persisting, myositis has not been reported. STUDY DESIGN: Case report. RESULTS: The patient is a 38 years old, HIV-negative male who developed sudden-onset fever up to 40.0 degrees C, headache, and sore eyes upon looking into light when on holidays in Thailand. One day after onset severe myalgias occurred in the shoulder girdle and hip girdle muscles. Clinical examination was normal, but blood work revealed elevated creatine-phosphokinase, glutamate-oxalate transaminase, and glutamate pyruvate transaminase, leucopenia and thrombocytopenia. Antibodies against Dengue viruses type 2 and 4 were positive and classical Dengue fever was diagnosed. The infection resolved upon symptomatic therapy, but myalgias, responsive only to opiates, resolved persistently not before the administration of corticosteroids, 2 months after onset. CONCLUSIONS: The case shows that Dengue fever may also cause persisting, severe, myositis for weeks, which do not respond to non-steroidal analgesics, but promptly to corticosteroids.

Adrenal Cortex Hormones↗

PubMed2006

Dengue-3 virus genomic differences that correlate with in vitro phenotype on a human cell line but not with disease severity.

We compared the full genome sequence of nine clinical isolates of dengue virus obtained during an epidemic of dengue-3 in French Polynesia in 1989, from patients with various presentations of disease. The isolates, all belonging to Genotype I, had 25 amino acid substitutions. There was no association with disease severity. When cultured in the K562 human erythroleukemia cell line, the isolates induced a range of cell growth inhibitions that was not associated with the degree of disease severity. By contrast, some substitutions--charge changes in NS1 and NS5, side-chain differences in NS1, loss of the E-153 potential glycosylation site, and 11 nucleotide insertions in the 3'UTR--that have been suggested to result in an increase or attenuation of dengue infection, appeared to be associated with the level of inhibition. These data represent the first documented study of an association between differences in the full dengue-3 genome of clinical isolates and the in vitro phenotype of these isolates on a human cell line.

Amino Acid Sequence↗