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PubMed1997

Antibody responses of dengue fever patients to dengue 2 (New Guinea C strain) viral proteins.

The present study was undertaken to investigate the antibody responses of dengue fever (DF) patients to specific dengue virus proteins. Partially purified dengue 2 New Guinea C (NGC) strain virus was used as antigen. Under the present experimental protocols, it was observed that almost all DF patients' sera had detectable presence of antibodies which recognize the dengue 2 envelope (E) protein. The convalescent-phase sera especially had significant detectable IgG, IgM and IgE against the protein. In addition, IgGs specific against the NS1 dimer and PrM were also detected. Antibody against the core (C) protein, however, was not detectable in any of the DF patients' sera. The substantial presence of IgG against the PrM in the convalescent-phase sera, and the presence of IgE specific for the E, reflect the potential importance of these antibody responses in the pathogenesis of dengue.

Antibodies, Viral↗
PubMed2003

Dengue viruses in the Caribbean. Twenty years of dengue virus isolates from the Caribbean Epidemiology Centre.

The first isolate of a dengue virus in the Americas was obtained in Trinidad and Tobago in 1953, and several dengue virus isolates were obtained in subsequent years. However, the systematic isolation and typing of dengue viruses in support of virus surveillance and outbreak investigations did not start until the creation of the Caribbean Epidemiology Centre (CAREC) in 1975. Since then, over two thousand viral isolates have been obtained and typed from many countries in the English and Dutch-speaking Caribbean. In this communication, virological data from 17 countries between 1977 and 1996 are presented and analyzed together for the first time with available epidemiological data. Types 1, 2 and 4 were isolated over the period, and geographic and temporal patterns in the distribution of the most prevalent strains are presented. The historical surveillance data is critically assessed. A temporal correlation with reported dengue incidence and rainfall data in Trinidad and Tobago is reported. Recent changes in epidemiological patterns are described, including reference to two large later outbreaks. Risk assessment of complicated forms of dengue virus infections in the Caribbean has been attempted, with some success. The importance of ongoing systematic surveillance is discussed.

Age Distribution↗
PubMed2005

Epidemiology of dengue and dengue hemorrhagic fever in a cohort of adults living in Bandung, West Java, Indonesia.

A prospective study of dengue fever (DF) and dengue hemorrhagic fever (DHF) was conducted in a cohort of adult volunteers from two textile factories located in West Java, Indonesia. Volunteers in the cohort were bled every three months and were actively followed for the occurrence of dengue (DEN) disease. The first two years of the study showed an incidence of symptomatic DEN disease of 18 cases per 1,000 person-years and an estimated asymptomatic/ mild infection rate of 56 cases per 1,000 person-years in areas of high disease transmission. In areas where no symptomatic cases were detected, the incidence of asymptomatic or mild infection was 8 cases per 1,000 person-years. Dengue-2 virus was the predominant serotype identified, but all four serotypes were detected among the cohort. Four cases of DHF and one case of dengue shock syndrome (DSS) were identified. Three of the four DHF cases were due to DEN-3 virus. The one DSS case occurred in the setting of a prior DEN-2 virus infection, followed by a secondary infection with DEN-1 virus. To our knowledge, this is the first report of a longitudinal cohort study of naturally acquired DF and DHF in adults.

Adult↗
PubMed2006

Circulating levels of tumour necrosis factor-alpha & interferon-gamma in patients with dengue & dengue haemorrhagic fever during an outbreak.

BACKGROUND & OBJECTIVE: Dengue haemorrhagic fever (DHF) is a severe illness caused by dengue viruses, the pathogenesis of which is not fully understood. Immune enhancement caused by cytokines, interferon and activated complement system is one of the hypotheses proposed to explain the haemorrhagic form of disease. This study was undertaken to investigate the role of pro-inflammatory cytokines tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) in dengue infection, and their possible association with disease severity. METHODS: Blood samples were collected from 60 patients; 28 patients of DF and 32 of DHF (clinically categorized into DF or DHF as per WHO criteria) from September to November 2003 at Delhi. Fifteen healthy individuals were included as control. All the patients were confirmed positive for dengue infection by serology or by reverse transcriptase-polymerase chain reaction (RT-PCR). Serum levels of TNF-alpha and IFN-gamma were determined by ELISA. RESULTS: The levels of both the cytokines were significantly elevated in the disease group as compared to the control group. Significantly higher levels of TNF-alpha; 258.02 pg/ml (P<0.005) were seen in patients having secondary infection, while patients with primary infection had higher level of IFN-gamma; 29.47 pg/ml (P<0.005). TNF-alpha was elevated in the later phase of illness, while IFN-gamma was elevated in early phase also. INTERPRETATION & CONCLUSION: Overproduction of TNF-alpha during secondary infection may have a role in immunopathogenesis of DHF, however, study of other cytokines produced along with IFN-gamma;, during the course of dengue infection is required to know the specific role of IFN-gamma in DI.

Adolescent↗
PubMed1975

Dengue virus replication in cultures of peripheral blood leukocytes during the course of dengue haemorrhagic fever.

A preliminary study was made of the ability of cultured human peripheral blood leukocytes (PBL) to support dengue 2 infection. Leukocyte donors, children hospitalized with primary (one case) or secondary dengue infections (12 cases), were studied during the acute and convalescent stages of illness. D2 virus replication occurred infrequently in PBL cultures obtained from children before the 10th day after onset of symptoms (2/23 samples), but frequently thereafter (8/13 samples). The absence of virus permissive cells during the acute stage of illness might be explained by several different mechanisms, including the possibility that permissive PBL are exhausted as the result of a severe dengue infection. An unexpected finding was the appearance of dengue hemagglutination-inhibition antibodies in cultures of PBL obtained from children during the acute stage of secondary dengue infections.

Acute Disease↗
PubMed2003

Why are dengue virus serotypes so distantly related? Enhancement and limiting serotype similarity between dengue virus strains.

Dengue virus, the causative agent of dengue fever, has four major serotypes characterized by large genetic and immunological distances. We propose that the unusually large distances between the serotypes can be explained in the light of a process of antibody-dependent enhancement (ADE) leading to increased mortality. Antibody-dependent enhancement results from a new infection with a particular serotype in an individual with acquired immunity to a different serotype. Classical dengue fever causes negligible mortality, but ADE leads to the risk of developing the significantly more dangerous dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS). A mathematical model is presented that describes the epidemiological dynamics of two serotypes of a pathogen where there is the possibility of co-infection and reinfection by a different serotype, along with increased mortality as a result of enhancement. We show that if there is no or slightly increased mortality after reinfection (enhancement), serotypes with a small immunological distance can stably coexist. This suggests that a cloud of serotypes with minor serological differences will constitute the viral population. By contrast, if enhancement is sufficiently great, a substantial immunological distance is necessary for two serotypes to stably coexist in the population. Therefore, high mortality owing to enhancement leads to an evolutionarily stable viral community comprising a set of distantly separated serotypes.

Antibody-Dependent Enhancement↗
PubMed1991

Activation of T lymphocytes in dengue virus infections. High levels of soluble interleukin 2 receptor, soluble CD4, soluble CD8, interleukin 2, and interferon-gamma in sera of children with dengue.

It has been reported that the severe complication of dengue virus infection, dengue hemorrhagic fever (DHF) is much more commonly observed during secondary dengue virus infections than primary infections. In order to elucidate the role of T lymphocytes in the pathogenesis of DHF, we attempted to determine whether T lymphocytes are activated in vivo during dengue virus infections, by examining the levels of soluble IL-2 receptor (sIL-2R), soluble CD4 (sCD4), soluble CD8 (sCD8), interleukin-2 (IL-2) and interferon-gamma (IFN gamma) in the sera of 59 patients with DHF and 41 patients with dengue fever (DF). The levels of sIL-2R, sCD4, sCD8, IL-2, and IFN gamma were significantly higher in the acute sera of patients with DHF than in the sera of healthy children (P less than 0.001 for all markers). The acute sera of patients with DF contained higher levels of sIL-2R, sCD4, IL-2, and IFN gamma than the sera of healthy children (P less than 0.001 for sIL-2R, IL-2, and IFN gamma; P less than 0.05 for sCD4), but did not have elevated levels of sCD8. The levels of sIL-2R (P less than 0.05), sCD4 (P less than 0.001), and sCD8 (P less than 0.001) were higher in DHF than in DF on days 3-4 after the onset of fever. The levels of IL-2 and IFN gamma in patients with DHF were highest 1 d before defervescence. There were no significant differences in the levels of sIL-2R, sCD4, sCD8, IL-2, and IFN gamma among grades 1, 2, and 3 of DHF. These results indicate (a) T lymphocytes are activated and produce IL-2 and IFN gamma in vivo during DHF and DF, (b) CD4+ T lymphocytes are activated in DHF and DF, and the level of activation is higher in DHF than in DF, and (c) activation of CD8+ T lymphocytes is evident in DHF, but not in DF.

Adolescent↗
PubMed2000

Failure of dengue-2 virus antibody to interfere with the isolation of dengue-2 virus from Aedes aegypti (Diptera: Culicidae).

When isolating dengue virus (DEN) from mosquitoes collected in endemic areas, pools may contain both anti-dengue antibodies from freshly engorged females and virus from DEN infected females. To determine if these antibodies may interfere with virus isolation, we simulated the isolation procedure using Aedes aegypti (L.) that we infected with the 16,681 strain of dengue type 2 virus by intrathoracic inoculation. At 7 d postinfection, we allowed females to engorge on immunized or normal mouse blood. Virus in a mixture of anti-dengue-2 antibodies and dengue-2 virus became inactive after incubation at 37 degrees C for 1 h, but remained infective without incubation. Therefore, at ambient conditions antibodies would not interfere with virus isolation from field-collected Ae. aegypti from endemic areas. In addition, DEN antibodies enhanced virus replication when inoculated into Ae. aegypti, but not C6/36 cells. The mechanism for this in vitro antibody enhancement of infection remains unclear.

Aedes↗
PubMed2004

Neonatal dengue infection: report of dengue fever in a 1-day-old infant.

A male infant was admitted because of fever. He was born at 37-weeks' gestation. His mother had experienced acute febrile illness with headache and myalgia. Her illness persisted with onset of active labor pain on day 5, which prompted cesarean section; postoperatively, the hematocrit decreased, requiring transfusion. The infant was well until fever developed at 16 hours after birth. There were petichiae on his face and trunk and the liver was enlarged. Fever subsided on day 5 without evidence of plasma leakage or severe hemorrhage. He made an uneventful recovery after 8 days of illness. Leukopenia and thrombocytopenia were present in the mother and infant. Both were diagnosed as dengue fever. Dengue type 1 was recovered from the infant by polymerase chain reaction. The dengue enzyme-linked immunoassay showed secondary infection in the mother and primary infection in the infant. In dengue-endemic areas, clinicians should be alert to dengue fever/dengue hemorrhagic fever in pregnant women presenting with acute febrile illness, and be prepared for proper management.

Adult↗
PubMed1990

Epidemic dengue 1 in Brazil, 1986: evaluation of a clinically based dengue surveillance system.

In the last 15 years, dengue fever has emerged as a major health problem in tropical America. Prevention and control of epidemic disease are enhanced by the rapid identification of new or increased dengue activity. Most surveillance systems, however, identify cases by clinical case reports and, therefore, lack the sensitivity needed for early detection. During the 1986 dengue 1 epidemic in Rio de Janeiro, Brazil, the authors evaluated the usefulness of a clinical case definition by comparing it with laboratory-confirmed infection status of residents in two cities. The case definition had a sensitivity of 64% and a false-positive rate of 57%. Thus, for every 100 laboratory-confirmed dengue infections, 230 cases were reported. Both infected and noninfected residents who used medical services and who lived in the city with the highest transmission were more likely to meet the case definition. Thus, factors unrelated to actual infection influenced the sensitivity. With the use of stepwise logistic regression, the authors analyzed combinations of patient symptoms and produced nine new hypothetical case definitions. However, none of the new definitions had a false-positive rate lower than 38%. This study emphasizes the need for laboratory-based dengue surveillance systems.

Adolescent↗
PubMed1989

[Active surveillance for dengue and dengue hemorrhagic fever].

Dengue and dengue hemorrhagic fever are emerging as major public health problems in most tropical countries. Effective prevention and control programs will depend on improved surveillance. A new approach to active surveillance is outlined with emphasis on the interepidemic period. The objective is to develop an early warning surveillance system than can predict epidemic dengue. Virologic surveillance is the most important in an early warning system. Dengue virus transmission should be monitored to provide information on which serotypes are present, their distribution, and the type of illness associated with each serotype. Other components of the active surveillance system include fever alert and clinical surveillance for severe and fatal disease associated with viral syndrome. Individually, each component is not very sensitive, but collectively, they provide an early warning capability that allows detection of newly introduced dengue virus serotypes well in advance of epidemic transmission. With such information, emergency mosquito control can be implemented and major epidemics averted.

Dengue↗
PubMed1989

Surveillance for dengue and dengue hemorrhagic fever.

Dengue and dengue hemorrhagic fever are emerging as major public health problems in most tropical countries. Effective prevention and control programs will depend on improved surveillance designed to provide early warning of dengue epidemics. This article outlines a reasonable approach to dengue surveillance of this kind. Virologic surveillance should be considered the most important element in any such early warning system. Dengue virus transmission should be monitored to determine which serotypes are present, their distribution, and the type of illnesses associated with each. Other key components of an active surveillance system should include monitoring of fever activity and clinical surveillance for cases of severe and fatal disease associated with viral syndromes. Collectively, these three surveillance components can provide an early warning capability permitting emergency mosquito control measures to be implemented and major epidemics to be averted.

Dengue↗
PubMed2002

Dengue-specific T cell responses in peripheral blood mononuclear cells obtained prior to secondary dengue virus infections in Thai schoolchildren.

Children who experience secondary dengue virus (DV) infections are at increased risk for dengue hemorrhagic fever. To study the effect of preexisting T cell responses to DV on the severity of secondary virus infection, peripheral blood mononuclear cells (PBMC) from 10 subsequently hospitalized and 12 nonhospitalized Thai schoolchildren were stimulated with inactivated dengue antigens, and proliferation of interferon (IFN)-gamma or tumor necrosis factor (TNF)-alpha responses of the preinfection PBMC were measured. Proliferation responses were observed in 11 subjects, and IFN-gamma responses were seen in 12 subjects, 6 of whom showed broad serotype cross-reactive IFN-gamma responses. TNF-alpha responses were detected exclusively in 4 hospitalized subjects. Four PBMC samples that showed neither proliferation nor cytokine responses to any dengue antigen were from nonhospitalized subjects. This study, thought to be the first to investigate T cell responses to DV in preinfection PBMC, suggests that the pattern of preexisting T cell responses influences the risk for severe disease.

Animals↗
PubMed2006

Implications of previous subclinical dengue infection but not virus load in dengue hemorrhagic fever.

In a study comparing the virus load and immune reaction between patients with primary and secondary dengue-2 (DEN-2) infections in a hospital-based analysis, we found that 40.7% (55/135) of the 135 patients had secondary DEN-2 infection following a DEN-2 outbreak in southern Taiwan. Most of the secondary infections had subclinical primary dengue infections (78.2%; 43/55). Patients with secondary DEN-2 infections had lower platelet counts, and blood interferon-alpha and virus load, but significantly higher interleukin-10 (P=0.030) and anti-DEN-1 neutralization titers (P=0.013) than those with primary infection. Patients with secondary DEN-2 infection also had a higher rate of dengue hemorrhagic fever (DHF) (61.7% vs. 36.3%). A previous subclinical dengue infection is involved in the secondary DEN-2 infection associated with altered immune reaction and higher DHF rate, but lower blood virus load.

Antibodies, Viral↗
PubMed2006

[Dengue and dengue hemorrhagic fever: research priorities].

Dengue is one of the most important infectious diseases in tropical and subtropical countries. At present, the only strategy available to reduce the incidence of dengue is vector control. The World Health Organization and the Pan American Health Organization have called on all nations to take the needed steps to help diminish the burden of this disease and its medical and socioeconomic impact. It is hoped that it will be possible to reverse the increase in dengue and help control its spread through a coordinated, effective international response, along with epidemiological, clinical, and virological research that brings together the most advanced methods and techniques. This piece summarizes the most up-to-date information on dengue, analyzes current epidemiologic trends in the Region of the Americas, discusses the main global and Western Hemisphere initiatives to control the disease, and presents the main areas of research that should be developed in the immediate future.

Adult↗
PubMed2006

Clinical characteristics of dengue and dengue hemorrhagic fever in a medical center of southern Taiwan during the 2002 epidemic.

BACKGROUND AND PURPOSE: This study investigated the clinical manifestations and risk factors for dengue fever (DF) and dengue hemorrhagic fever (DHF) and disease severity during the 2002 outbreak in the Kaohsiung area. METHODS: We analyzed the clinical characteristics of 644 patients with virologically or serologically positive results for dengue virus at Kaohsiung Medical University Hospital from January 1 to December 31, 2002. RESULTS: The case rate peaked in November. The male-to-female ratio was 1:1.2 and the mean age was 47.5 +/- 17.9 years (range, 7 months to 88 years). The criteria for DHF were fulfilled in 232 cases, including 12 cases of dengue shock syndrome (DSS). The most common symptoms were fever (96.1%), myalgia (68.5%), headache (55.4%), and skin rash (53.7%). Hemorrhagic manifestations were noted in 73.0% of patients. The mean age of patients with DHF/DSS was 53.6 +/- 16.3 years, and the highest incidence occurred in those aged 60-69 years (27.2%). Significant risk factors for DHF/DSS were age >65 years, diabetes mellitus, hypertension, and uremia. Gallbladder wall thickening was found in 64.7% of DHF cases who underwent abdominal ultrasound examination. 164 of the 232 DHF cases (71%) were discharged without a diagnosis of DHF. The number of DHF cases identified by our study was nearly equal to that reported through the established passive surveillance system (232 cases vs 242). CONCLUSIONS: DHF was under-reported in hospital, suggesting that continuous surveillance and education for clinicians in the recognition of DHF, especially in elderly patients and those with chronic pre-existing comorbidities, is needed.

Academic Medical Centers↗
PubMedDate not supplied

Dengue fever and dengue haemorrhagic fever: challenges of controlling an enemy still at large.

Dengue virus infections are a serious cause of morbidity and mortality in most tropical and subtropical areas of the world: mainly Southeast and South Asia, Central and South America, and the Caribbean. Understanding the pathogenesis of dengue haemorrhagic fever (DHF), the severe form of dengue illness, is a very important and challenging research subject. Viral virulence and immune responses have been considered as two major factors responsible for the pathogenesis. Virological studies are attempting to define the molecular basis of viral virulence. The immunopathological mechanisms appear to include a complex series of immune responses. A rapid increase in the levels of cytokines and chemical mediators apparently plays a key role in inducing plasma leakage, shock and haemorrhagic manifestations. It is likely that the entire process is initiated by infection with a so-called virulent dengue virus, often with the help of enhancing antibodies in secondary infection, and then triggered by rapidly elevated cytokines and chemical mediators produced by intense immune activation. However, understanding of the DHF pathogenesis is not complete. We still have a long way to go.

Animals↗