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[Epidemiology of dengue and hemorrhagic dengue in Santiago, Cuba 1997].

A dengue epidemic that Cuba reported in 1997 registered more than 500,000 cases of dengue fever produced by viral serotype 1. In 1981, there was an epidemic of dengue hemorrhagic fever produced by serotype 2 of the virus. This time 344,203 clinical cases were reported, 10,312 of which were severe cases of hemorrhagic fever that led to 158 fatalities (101 of them among children). The reintroduction of dengue, and specifically of dengue viral serotype 2 (Jamaica genotype), was quickly detected in January 1997 through an active surveillance system with laboratory confirmation of cases in the municipality of Santiago de Cuba, in the province of the same name. The main epidemiological features of this outbreak are reported in this paper. A total of 3,012 cases were reported and serologically confirmed. These included 205 cases classified as dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), 12 of which were case fatalities (all among adults). Secondary infection with dengue virus was one of the most important risk factors for DHF/DSS. Ninety-eight percent of the DHF/DSS cases and 92% of the fatal cases had contracted a secondary infection. It was the first time dengue hemorrhagic fever was documented as a secondary infection 16 to 20 years after initial infection. Belonging to the white racial group was another important risk factor for DHF/DSS, as had been observed during the 1981 epidemic. During the most recent epidemic it was demonstrated that the so called "fever alert" is not useful for early detection of an epidemic. Measures taken by the country's public health officials prevented spread of the epidemic to other municipalities plagued by Aedes aegypti.

Adolescent↗

The status of dengue fever virus in South Africa--serological studies and diagnosis of a case of dengue fever.

To assess the possibility of a dengue epidemic occurring in South Africa 3 groups of survey sera and 2 groups of patients' sera, from a dengue high risk area of South Africa, were tested for antibodies to several flaviviruses. 3.8% (75/1951) of the survey sera and 9.2% (26/282) of the patients' sera had haemagglutination inhibition antibodies to one or more of the flaviviruses tested. One of 1951 survey sera had a spectrum of complement fixation antibody consistent with a primary dengue infection, and 5 of 282 patients' sera also had complement fixation antibodies to flavivirus antigens. These 5 positive patients had recently travelled to India but in only one was there an antibody spectrum unequivocably consistent with a primary dengue infection. Dengue virus type 1 was successfully isolated from this patient's acute serum. The susceptibility of the population to dengue virus infection, the presence of the main vector of dengue virus and the occurrence of imported cases of dengue fever emphasize the need for continuous vigilance.

Antibodies, Viral↗

[The epidemic of dengue and hemorrhagic dengue fever in the city of Rio de Janeiro, 2001/2002].

The following study was intended to evaluate the occurrence of typical signs and symptoms in the cases of classic dengue and hemorrhagic dengue fever, during the 2001-2002 epidemic in the city of Rio de Janeiro. The authors reviewed 155,242 cases notified to the Information System of Notification Diseases, from January/2001 to June/2002: 81,327 cases were classified as classic dengue and 958 as hemorrhagic dengue fever, with a total of 60 deaths. Common symptoms, such as fever, headache, prostration, myalgia, nausea and retro-orbital pain, had a high incidence in both classic and hemorrhagic dengue fever. On the other hand, hemorrhagic signs and other signs of severe disease, such as shock, gastrointestinal bleeding, petechiae, epistaxis, abdominal pain and pleural effusion, were strongly associated to hemorrhagic dengue fever. Besides, the occurrence of death was 34.8 times higher in hemorrhagic dengue fever than in classic dengue (OR = 34.8; CI 19.7-61.3).

Brazil↗

The dual-specific binding of dengue virus and target cells for the antibody-dependent enhancement of dengue virus infection.

Using flow cytometric assay and monoclonal anti-dengue Ab, we observed that both anti-E and anti-prM Abs could enhance dengue virus infection in a concentration-dependent but serotype-independent manner. Increases were found in both the percentage of dengue-infected cells and the expression of dengue E and NS1 protein per cell. Dengue virion binding and infection were enhanced on FcR-bearing cells via the Fc-FcgammaRII pathway. Furthermore, anti-prM Ab also enhanced dengue virion binding and infection on cells lacking FcR, such as BHK-21 or A549 cells, by the mechanism of peptide (CPFLKQNEPEDIDCW)-specific binding. Anti-prM Ab cross-reacted with BHK-21 or A549 cells and recognized self-Ags such as heat shock protein 60. In summary, a novel mechanism of anti-prM Ab-mediated enhancement on dengue virus infection was found to be mediated by dual specific binding to dengue virion and to target cells, in addition to the traditional enhancement on FcR-bearing cells.

Amino Acid Sequence↗

Dengue in Greece in 1927 and 1928 and the pathogenesis of dengue hemorrhagic fever: new data and a different conclusion.

A massive outbreak of dengue, with a high incidence of hemorrhagic manifestations and a high death rate, occurred in Athens and neighboring areas of Greece in 1927 and 1928. For many years it was believed that the episode had been caused by dengue type 1 virus. Recently, it was claimed that dengue type 2 virus also was present in Athens in 1928, and this report is cited in support of the hypotheses that dengue hemorrhagic fever is almost always the result of sequential infection with different dengue serotypes and that infection with dengue type 2 following dengue type 1 is particularly pathogenic. In the present study of 258 Greek residents born from 1914 to 1938, it was also found that dengue type 2 had occurred in Greece--but after 1928. No evidence was found that that virus had occurred in the country during, or within 13 years before, the 1927-1928 epidemic.

Aged↗

Short report: immune response and occurrence of dengue infection in thai children three to eight years after vaccination with live attenuated tetravalent dengue vaccine.

From 1992 to 1997, 140 Thai children 4-15 years of age received an investigational live attenuated tetravalent dengue vaccine (LATDV). These children were contacted 3-8 years later in 2001 to assess humoral immunity and investigate whether they were subsequently at higher risk of developing severe dengue. One hundred thirteen were successfully contacted and participated in this retrospective cohort study with two age- and address-matched controls per vaccinee. The number of vaccinated subjects with neutralizing antibodies increased compared with 3-8 years earlier, which was probably due to subsequent wild-type dengue infections. There were no excess hospitalizations for clinically suspected dengue fever (DF) or dengue hemorrhagic fever (DHF) in vaccinees (one with DF and three with DHF) compared with controls (14 with DHF). Results suggest that preexisting dengue antibodies induced by LATDV do not enhance dengue illness, and the use of the vaccine in a dengue-endemic area is safe.

Adolescent↗

Quantitation of T lymphocyte subsets helps to distinguish dengue hemorrhagic fever from classic dengue fever during the acute febrile stage.

Activation of immunoregulatory T lymphocyte subsets has been observed in dengue viral infection, being more evident in dengue hemorrhagic fever (DHF) than in classical dengue fever (DF). There are, however, as yet no well-defined host markers to determine which patients with dengue viral infection will develop severe complications during the acute febrile stage of the disease. A study was performed to compare the cellular immune status in DHF, DF and non-dengue viral infections (NDF) in order to determine the value of these parameters in distinguishing DHF from classic DF and other viral infections during the acute febrile stage of the disease. This study involved 109 febrile patients admitted because of suspected DHF. Fifty patients were serologically confirmed cases of dengue infection, of which 25 had grade 1 or 2 DHF. There was a reduction in total T (CD3), CD4 and CD8 cells in DHF and demonstrated that a low level of CD3, CD4, CD8 and CD5 cells discriminated DHF from DF patients during the febrile stage of the illness. In contrast, B (CD19) cells and natural killer (NK) cells did not appear to be discriminatory in this study. Receiver operating characteristic (ROC) curve analysis showed that a combination of CD3 cell of < or = 45% and CD5 cell of < or = 55% was the best marker to identify DHF patients (sensitivity = 84% and specificity = 52% for CD3 cell of < or = 45%; sensitivity = 92% and specificity = 71% for CD5 cell of < or = 55%). CD4 cell of < or = 25% and CD8 cell < or = 30% were equally good in discriminating DHF from DF patients. On the other hand, the ROC curves indicated no clear difference between the immunoregulatory cell counts in DF from NDF Lymphopenia, atypical lymphocytosis and thrombocytopenia were significantly more evident in dengue compared to non-dengue infection but did not appear to be discriminatory among DHF and DF patients. The reduction in CD3, CD4, CD8, CD5 cells correlated with the degree of thrombocytopenia in DHF (p < 0.05) which suggests that these cells probably participate in a common pathogenetic mechanism.

Acute Disease↗

Concurrent infections by two dengue virus serotypes among dengue patients in Taiwan.

The co-circulation of multiple dengue virus serotypes in the same region has been reported in several countries in Southeast Asia as well as in Central and South America for decades. Although outbreaks involving more than one serotype of dengue virus have been reported in Taiwan since 1987, concurrent infection in the same individual by multiple serotypes of dengue virus have never been identified. Using a modified multiplex reverse transcription-polymerase chain reaction assay, we detected and determined the serotypes of 21 dengue patients during an outbreak in southern Taiwan in 2000. While either dengue type 2 or type 3 virus was found in most cases, 2 of the 21 cases were concurrent infections by both dengue type 2 and dengue type 3 viruses. This was further confirmed by sequence analysis of the amplified products. This study reports for the first time that concurrent infections occur in Taiwan, and suggests that future virologic surveillance of dengue outbreak in Taiwan should take this into consideration.

Base Sequence↗

Isolation and serotyping of dengue viruses by mosquito inoculation technique from clinically suspected cases of dengue fever.

Dengue virus was isolated from 44 clinically suspected cases of dengue fever by mosquito inoculation technique using Aedes aegypti mosquito in the department of virology, BSMMU in the year 2000. Identification of dengue virus was done by direct fluorescent antibody technique using FITC conjugated anti-dengue monoclonal antibody and serotyping was carried out by indirect fluorescent antibody technique using serotype specific monoclonal anti-dengue antibody. The dengue virus isolation rate was 41.9%. The result of serotyping revealed circulation of all four serotypes of dengue viruses in Dhaka, Bangladesh and DEN-3 was the predominant (70.5%) serotype during the outbreak in 2000. The rate of isolation was higher in patient's serum at an early stage of fever (p<0.01) and with higher body temperature (p<0.01). The rate of isolation was 77.77% in patient's serum collected on the 1st day of fever, and then the rate gradually declined and lowest (16.6%) on the 5th day of fever. The mosquito inoculation technique is an easy, economical and sensitive method for dengue virus isolation and is recommended for routine virological surveillance in laboratories of Bangladesh where sophisticated facilities are limited.

Adolescent↗

Dengue fever and dengue haemorrhagic fever--a diagnostic challenge.

The number of cases of dengue fever in returning travellers is increasing worldwide. In Australia, two mosquito vectors exist and the Aedes aegypti mosquito has already been responsible for local transmission within Queensland. For these reasons, general practitioners need to be able to recognise dengue fever and its complications: dengue haemorrhagic fever (DHF) and dengue shock syndrome. Infections can vary from severe to asymptomatic. The incubation period, duration of fevers, presence of rash and relative bradycardia can assist in the diagnosis of dengue. Dengue haemorrhagic fever is a severe form of dengue fever associated with plasma leakage and specific risk factors. The risk of DHF to most travellers previously infected with dengue is probably low. Serology and reverse transcriptase polymerase chain reaction are useful tests for diagnosing infection, although both have limitations. Vaccine design is a promising strategy to prevent infection.

Adult↗

Double infection of heteroserotypes of dengue viruses in field populations of Aedes aegypti and Aedes albopictus (Diptera: Culicidae) and serological features of dengue viruses found in patients in southern Thailand.

In order to understand more about the epidemiology of DHF, a study of the type of dengue viruses and vectors under natural conditions was carried out. Mosquito vectors in the field and the serum of DHF patients in southern Thailand were examined. The two mosquito species are abundant and DHF incidence remains high in this region. Dengue viruses were examined in field-caught mosquitoes by RT-PCR technique. The mosquitoes were caught in 4 provinces: Krabi, Phuket, Phang-Nga and Surat Thani during the late dry season until the early rainy season in 2005. Three dengue serotypes (DEN-2, DEN-3, DEN-4) were detected in Ae. aegypti males and females, and 2 (DEN-2, DEN-3) were detected in Ae. albopictus females. Double infection with 2 serotypes of dengue viruses (DEN-2 and DEN-3) were detected in Ae. aegypti males and females and Ae. albopictus females. DEN-2 and DEN-1 were the most prevalent serotypes found in the serum of the patients in this area, followed by DEN-4 and DEN-3. The prevalence of the predominant dengue serotype varied from province to province. Detection of viruses in adult male mosquitoes reveals the role of transovarial transmission of dengue viruses in field populations of DHF vectors and elucidates circulation of dengue viruses in vectors in the natural environment of endemic areas. The incidence of multiple serotypes of dengue virus in Ae. aegypti and Ae. albopictus in the same area points toward a high risk for an epidemic of DHF. These findings provide greater understanding of the relationship among mosquito vectors, virus transmission and DHF epidemiology in endemic areas.

Aedes↗

[Dengue fever and hemorrhagic dengue in infants with a primary infection].

The aim of this work was to offer a description of the clinical manifestations developed by patients under 1 year who had dengue virus infection and dengue hemorrhagic fever during the epidemic which broke out in 1981, and to determine if the passive transfer of maternal dengue antibodies to the fetuses influenced the occurrence of a severe development of the disease, through a retrospective study. In 20 cases, type 2 dengue virus infection was confirmed. Eight patients showed the clinical manifestations of dengue hemorrhagic fever of dengue shock syndrome (DHF/DSS), and the other 12 had the typical dengue virus infection. The former were of the white racial phenotype, aged under 6 months. There was a predominance of type 1 dengue antibodies in the mothers of children with DHF/DSS. Fever, rash, vomiting and diarrheas (not frequent) appeared in the two clinical manifestations of the infection; blood leukocytes were predominantly lymphocytic; and erythrocyte sedimentation was always normal. Patients with DHF/DSS presented with some bleeding (87.5%); cyanosis and ascites (37.5%); and shock (25%), as well as hepatomegaly. All these infants with DHF/DSS had thrombocytopenia and most of them showed hemoconcentration. No deaths occurred.

Adult↗

Don't forget dengue! Clinical features of dengue fever in returning travellers.

BACKGROUND: Dengue virus infection is an increasingly important cause of imported fever, but many cases remain unrecognised. This study reviews the clinical features of dengue fever in patients seen at a regional department of infection and tropical medicine. SUBJECTS: All patients with dengue fever presenting to the Department of Infection and Tropical Medicine in Leicester over a three year period. RESULTS: The diagnosis of dengue fever was confirmed in 15 patients. The age range of patients was 19-61 years, and 80% were immigrants returning from a visit to their country of origin. In 11 (73%) patients, infection was associated with travel to India; others had gone to South-east Asia, Barbados and Uganda. All patients presented within three weeks of their return to the United Kingdom. The clinical manifestations of infection were often non-specific. They included fever, nausea, headache, cough and diarrhoea; 5 (33%) patients had a macular rash. Thrombocytopenia was seen in 7 (47%) patients, but only one had evidence of dengue haemorrhagic fever. Dengue infection was confirmed by serology in 14 (93%) patients. In one, dengue virus type 1 was identified by polymerase chain reaction, and the virus was subsequently isolated in tissue culture. CONCLUSIONS: Dengue virus infection should be considered in all febrile travellers who have recently returned from areas where the disease is endemic and in whom tests for malaria are negative.

Adult↗

Proinflammatory factors present in sera from patients with acute dengue infection induce activation and apoptosis of human microvascular endothelial cells: possible role of TNF-alpha in endothelial cell damage in dengue.

There is evidence that severe dengue disease is associated with alterations of the microvascular endothelium. We examined the hypothesis that activation and damage of microvascular endothelial cells (EC) could be induced by inflammatory mediators present in dengue patient's sera. We cultured human microvascular EC (HMEC-1) in vitro with sera from patients with acute dengue infection. Sera from patients with acute dengue induced an increase in ICAM-1 expression on HMEC-1. This effect was greater with samples from the acute febrile phase than with samples from the convalescent phase of the disease. Acute dengue sera had elevated levels of TNF-alpha and the endothelial activating effect of acute dengue sera was inhibited up to 80% by pre-treatment with monoclonal antibodies against TNF-alpha. Furthermore, acute dengue sera induced apoptosis in HMEC-1. These findings support the pathophysiologic significance of microvascular EC and serum inflammatory mediators in dengue.

Apoptosis↗

An enzyme-linked immunosorbent assay using a chaotropic agent (sodium thiocyanate) for serotype specific reaction between crude dengue viral antigen and anti-dengue mouse antibody.

An enzyme-linked immunosorbent assay (ELISA) has been developed to detect serotype specific reaction between crude dengue viral antigen and anti-dengue mouse hyperimmunized antibody under the stringent condition in the presence of a Chaotropic agent, sodium thiocyanate (NaSCN), in the reaction mixture of antigen and antibody. Rapidly sedimenting hemagglutinin (RHA) derived from type 2 dengue virus-infected mosquito cell culture fluid reacted to the antibody for both type 2 and type 3 dengue viruses in the ELISA. In contrast, its reactivity was reduced after the addition of NaSCN in the ELISA. Soluble complement-fixing antigen (SCF) derived from type 2 dengue virus-infected mosquito cell culture fluid reacted serotype specifically to anti-dengue type 2 antibody, and was relatively stable for the NaSCN treatment in the ELISA. Anti-type 2 RHA mouse antibody reacted to both type 1 and type 2 dengue viral antigens and its reactivity was reduced after the addition of NaSCN in the ELISA. Anti-type 2 SCF antibody reacted serotype specifically to type 2 dengue viral antigen with and without NaSCN in the ELISA.

Animals↗

Murine immunoglobulin G subclass responses following immunization with live dengue virus or a recombinant dengue envelope protein.

Murine immunoglobulin G (IgG) subclass responses to immunization are restricted to certain subclasses depending on the nature of the immunogen. Immunization with live viruses generally leads to a predominant IgG2a response, which may be the most effective at resisting future challenge due to the unique effector functions of IgG2a. Knowledge of subclass responses following immunization with dengue vaccine candidates may be helpful in determining which candidates are most efficacious. We measured the dengue-specific IgG subclass responses of BALB/c mice following immunization with live dengue-2 virus or with a partially purified recombinant dengue-2 envelope (E) protein. Subclass responses following immunization with live virus were IgG2a > IgG1 > IgG2b > IgG3, as opposed to IgG1 > IgG2a > IgG2b > IgG3 after immunization with recombinant protein. Responses of all subclasses except IgG1 were greater following immunization with live dengue than with the recombinant E protein. Neutralizing antibody titers were also higher after immunization with live virus than with E protein and were positively correlated with dengue-specific IgG2a responses in mice immunized with recombinant E protein. Following separation of the four IgG subclasses by chromatography, the IgG2a fraction exhibited the greatest neutralizing activity. The results seen after immunization with live dengue virus or recombinant E protein in this study are in concordance with studies involving other viruses and viral proteins and may have implications for the development of an effective vaccine for dengue.

Animals↗