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Showing papers on "Dengue fever published in 1989"


Journal ArticleDOI
TL;DR: It is proposed that measurement of dengue and Japanese encephalitis IgM and IgG antibodies upon admission and discharge from hospital care should replace the hemagglutination inhibition assay as the standard d Dengue serologic technique in regions where these 2 viruses co-circulate.
Abstract: The diagnostic sensitivity and specificity of detection of anti-dengue IgM by antibody capture enzyme-linked immunosorbent assay (ELISA) was investigated in dengue infections in a variety of clinical settings. Sera from uninfected controls were uniformly negative. Serial specimens from experimental and natural infections showed that viremia and fever terminated as anti-dengue IgM became detectable. Anti-dengue IgM appeared in most cases by the 3rd afebrile day of illness and declined to undetectable levels after 30-60 days. Assay sensitivity was 78% in admission sera (924/1,183; 95% CI = 75-81%) and 97% in paired sera (1,030/1,062; 95% CI = 96-98%) thus exceeding or matching the performance of the hemagglutination-inhibition assay. Measurement of the anti-dengue IgM to anti-Japanese encephalitis IgM ratio correctly identified all sera from 112 patients with strictly defined Japanese encephalitis and 98% (307/312; 95% CI = 96-99%) of sera from patients whose dengue infections were confirmed by virus isolation. Dengue infections could be classified as primary or secondary by determining the ratio of units of dengue IgM to IgG antibody. We propose that measurement of dengue and Japanese encephalitis IgM and IgG antibodies upon admission and discharge from hospital care should replace the hemagglutination inhibition assay as the standard dengue serologic technique in regions where these 2 viruses co-circulate.

704 citations


Journal ArticleDOI
TL;DR: High serum DEN-2 antibody dependent enhancing activity is a significant (relative risk = 6.2) risk factor for severe illness among children in a dengue hemorrhagic fever endemic region.
Abstract: Serum specimens collected during a prospective study of dengue infections among schoolchildren in Bangkok were tested for their ability to enhance dengue 2 (DEN-2) virus growth in human monocytes in vitro. Two groups of dengue-immune sera were compared: 32 dengue antibody positive serum specimens from children who subsequently developed asymptomatic secondary dengue infections; and 9 dengue antibody positive serum specimens from children who subsequently developed severe symptomatic secondary dengue infections, 8 of which were clinically diagnosed as dengue hemorrhagic fever. Antibody-dependent enhancement of virus growth was quantitated by measurement of virus yields in supernatant fluids of normal human monocyte cultures that were infected with DEN-2 virus in the presence of undiluted test serum. Only 4 of 32 (12%) preinfection sera from asymptomatic children, but 6 of 9 (67%) preinfection sera from symptomatic children, had significant enhancing activity (P < 0.001). High serum DEN-2 antibody dependent enhancing activity is a significant (relative risk = 6.2) risk factor for severe illness among children in a dengue hemorrhagic fever endemic region. Dengue antibodies can be neutralizing and therefore protective, or they can be enhancing and increase the risk of dengue hemorrhagic fever.

507 citations


Journal ArticleDOI
TL;DR: It will be of interest to establish whether other viral hemorrhagic fevers involve the same target cells as in DHF/DSS and are mediated by similar effector mechanisms.
Abstract: Dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) in children is reliably associated with the presence of dengue antibody--actively or passively acquired--before the onset of illness. Limited observations by electron microscopy and fluorescent antibody testing and the recovery of virus from tissues obtained at autopsy show that dengue viruses are consistently associated with cells of mononuclear phagocyte lineage. In particular, virus is associated with Kupffer cells, pulmonary macrophages, and mononuclear cells in skin and blood. Endothelial cells fail to demonstrate necrosis or inflammatory changes. Since acute vascular permeability, shock, and hemorrhage occur late in illness, a plausible hypothesis is that phlogistic factors, resulting from interactions with elements of the immune response, are released from virus-infected mononuclear phagocytes. Such phenomena as generalized depression of mitotic activity of bone marrow cells, destruction of mature polymorphonuclear leukocytes, complement activation, and abnormal hemostasis may serve as markers of these phlogistic factors. It will be of interest to establish whether other viral hemorrhagic fevers involve the same target cells as in DHF/DSS and are mediated by similar effector mechanisms.

447 citations


Journal Article
TL;DR: The article summarizes the main clinical, virological, and epidemiological data obtained during the outbreak of dengue haemorrhagic fever, some of which are reported for the first time.
Abstract: Dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS) is one of the principal causes of hospitalization and death among children in several south-east Asian countries. Also, in the Region of the Americas, there has been an increase in the frequency of dengue fever epidemics and in the number of cases of DHF/DSS. In 1981 an epidemic of dengue haemorrhagic fever occurred in Cuba and this suggests that there is a high risk that such epidemics could recur in the region. The article summarizes the main clinical, virological, and epidemiological data obtained during the outbreak, some of which are reported for the first time.

352 citations


01 Jan 1989
TL;DR: Based on the observation of 11 patients (10 males and 1 female), the occurrence of hemorrhagic fever with renal syndrome in two new geographic areas of Romania is reported, two patients died within several hours after admission and four patients recovered gradually.
Abstract: Hantaviruses, the causative agents of HFRS, have become more widely recognized. Epidemiologic evidence indicates that these pathogens are distributed worldwide. People who come into close contact with infected rodents in urban, rural and laboratory environments are at particular risk. Transmission to man occurs mainly via the respiratory tract. The epidemiology of the hantaviruses is intimately linked to the ecology of their principal vertebrate hosts. Four distinct viruses are now recognized within the hantavirus genus and that number is likely to increase to six very soon; however, further investigations are necessary. Much more work is still needed before we fully understand the wide spectrum of clinical signs and symptoms of HFRS as well as the pathogenicity of the different viruses in the hantavirus genus of the Bunyaviridae family. HFRS is difficult to diagnose on clinical grounds alone and serological evidence is often needed. A fourfold rise in IgG antibody titer in a 1-week interval, and the presence of the IgM type of antibodies against hantaviruses are good evidence for an acute hantavirus infection. Physicians should be alert for HFRS each time they deal with patients with acute febrile flu-like illness, renal failure of unknown origin and sometimes hepatic dysfunction. Especially the mild form of HFRS is difficult to diagnose. Acute onset, headache, fever, increased serum creatinine, proteinuria and polyuria are signs and symptoms compatible with a mild form of HFRS. Differential diagnosis should be considered for the following diseases in the endemic areas of HFRS: acute renal failure, hemorrhagic scarlet fever, acute abdomen, leptospirosis, scrub typhus, murine typhus, spotted fevers, non-A, non-B hepatitis, Colorado tick fever, septicemia, dengue, heartstroke and DIC. Treatment of HFRS is mainly supportive. Recently, however, treatment of HFRS patients with ribavirin in China and Korea, within 7 days after onset of fever, resulted in a reduced mortality as well as shortened course of illness.

229 citations


Journal ArticleDOI
TL;DR: In this article, the authors analyzed clones of Dengue serotype crossreactive T lymphocytes derived from the PBMC of a donor who had been infected with dengue 3 virus.
Abstract: The severe complications of dengue virus infections, hemorrhagic manifestation and shock, are much more commonly observed during secondary infections caused by a different serotype of dengue virus than that which caused the primary infections. It has been speculated, therefore, that dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are caused by serotype crossreactive immunopathological mechanisms. We analyzed clones of dengue serotype crossreactive T lymphocytes derived from the PBMC of a donor who had been infected with dengue 3 virus. These PBMC responded best to dengue 3 antigen, but also responded to dengue 1, 2, and 4 antigens, in bulk culture proliferation assays. 12 dengue antigen-specific clones were established using a limiting dilution technique. All of the clones had CD3+ CD4+ CD8 phenotypes. Eight clones responded to dengue 1, 2, 3, and 4 antigens and are crossreactive, while four other clones responded predominantly to dengue 3 antigen. These results indicate that the serotype crossreactive dengue-specific T lymphocyte proliferation observed in bulk cultures reflects the crossreactive responses detected at the clonal level. Serotype crossreactive clones produced high titers of IFN-gamma after stimulation with dengue 3 antigens, and also produced IFN-gamma to lower levels after stimulation with dengue 1, 2, and 4 antigens. The crossreactive clones lysed autologous lymphoblastoid cell line (LCL) pulsed with dengue antigens, and the crossreactivity of CTL lysis by T cell clones was consistent with the crossreactivity observed in proliferation assays. Epidemiological studies have shown that secondary infections with dengue 2 virus cause DHF/DSS at a higher rate than the other serotypes. We hypothesized that the lysis of dengue virus-infected cells by CTL may lead to DHF/DSS; therefore, the clones were examined for cytotoxic activity against dengue 2 virus-infected LCL. All but one of the serotype crossreactive clones lysed dengue 2 virus-infected autologous LCL, and they did not lyse uninfected autologous LCL. The lysis of dengue antigen-pulsed or virus-infected LCL by the crossreactive CTL clones that we have examined is restricted by HLA DP or DQ antigens. These results indicate that primary dengue virus infections induce predominantly crossreactive memory CD4+ T lymphocytes. These crossreactive T lymphocytes proliferate and produce IFN-gamma after stimulation with a virus strain of another serotype, and demonstrate crossreactive cyotoxic activity against autologous cells infected with heterologous dengue viruses.(ABSTRACT TRUNCATED AT 400 WORDS)

149 citations


Journal ArticleDOI
TL;DR: Results indicate that PBMC from dengue-immune donors contain CD4+ T cells that proliferate and produce IFN gamma after stimulation with d Dengue antigens, and suggest that the IFN Gamma that is produced by these stimulated dengu-specific T cells may contribute to the pathogenesis of dengued hemorrhagic fever and denge shock syndrome.
Abstract: The severe complications of dengue virus infections, hemorrhagic manifestations and shock, are more commonly observed during secondary dengue virus infections than during primary infections. It has been speculated that these complications are mediated by cross-reactive host-immune responses. We have begun to analyze human T cell responses to dengue antigens in vitro to explain the possible role of T lymphocytes in the pathogenesis of these complications. Dengue antigens induce proliferative responses of PBMC from dengue antibody-positive donors, but do not induce specific proliferative responses of PBMC from dengue antibody-negative donors. IFN gamma is detected in the culture fluids of dengue-immune PBMC stimulated with dengue antigens. The cells that proliferate in the dengue antigen-stimulated bulk cultures have CD3+, CD4+, CD8-, CD16-, and CD20- phenotypes. Dengue-specific T cell lines were established using limiting dilution techniques. They have CD3+, CD4+, and CD8- phenotypes, and produce IFN gamma in response to dengue antigens. Culture fluids from dengue-immune PBMC stimulated with dengue antigens, which contain IFN gamma, augment dengue virus infection of human monocytes by dengue virus-antibody complexes. These results indicate that PBMC from dengue-immune donors contain CD4+ T cells that proliferate and produce IFN gamma after stimulation with dengue antigens, and suggest that the IFN gamma that is produced by these stimulated dengue-specific T cells may contribute to the pathogenesis of dengue hemorrhagic fever and dengue shock syndrome by increasing the number of dengue virus-infected monocytes in the presence of cross-reactive anti-dengue antibodies.

141 citations


Journal ArticleDOI
TL;DR: Because of the lack of pathologic findings in major organs and the rapid recovery (without sequelae) of survivors, physiologic dysfunction is thought to be secondary to the action of biologic mediators that are capable of producing severe illness with minimal structural injury.
Abstract: Dengue hemorrhagic fever is characterized by a sudden onset of fever that lasts for 2-7 days and then subsides, at which time hemorrhagic manifestations become evident. Sometimes there is an associated form of hypovolemic shock known as dengue shock syndrome. There are usually significant changes in the liver, the reticuloendothelial system, and the vascular system (e.g., necrosis of liver cells and focal hemorrhage, increase in turnover of lymphocytes, and diapedesis of erythrocytes through vessel walls). Because of the lack of pathologic findings in major organs and the rapid recovery (without sequelae) of survivors, physiologic dysfunction is thought to be secondary to the action of biologic mediators that are capable of producing severe illness with minimal structural injury.

117 citations


Journal ArticleDOI
01 Sep 1989-Blood
TL;DR: It is shown that dengue type 4 (DEN4) propagates in colonies derived from immature human bone marrow progenitors and was efficiently propagated in human hematopoietic cell lines, especially those with erythroid properties.

105 citations


Journal ArticleDOI
TL;DR: Dengue viruses types 2 or 3 were recovered from the liver of 5 out of 17 children who were suspected to have died of dengue and it is suggested that the pathogenesis of the two diseases may be analogous.

104 citations


Journal ArticleDOI
TL;DR: It is suggested that serotype-cross-reactive CD8+ CTL may be important mediators of viral clearance and of virus-induced immunopathology during secondary dengue virus infections.
Abstract: Stimulation with live dengue virus of peripheral blood mononuclear cells from a dengue virus type 4-immune donor generated virus-specific, serotype-cross-reactive, CD8+, class I-restricted cytotoxic T lymphocytes (CTL) capable of lysing dengue virus-infected cells and cells pulsed with dengue virus antigens of all four serotypes. These CTL lysed autologous fibroblasts infected with vaccinia virus-dengue virus recombinant viruses containing the E gene or several nonstructural dengue virus type 4 genes. These results demonstrate that both dengue virus structural and nonstructural proteins are targets for the cytotoxic T-cell-mediated immune response to dengue virus and suggest that serotype-cross-reactive CD8+ CTL may be important mediators of viral clearance and of virus-induced immunopathology during secondary dengue virus infections.

01 Jan 1989
TL;DR: A reasonable approach to dengue surveillance of this kind is outlined, which can provide an early warning capability permitting emergency mosquito control measures to be implemented and major epidemics to be averted.
Abstract: 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.

Journal ArticleDOI
TL;DR: Hemorrhagic fever viruses are found in both temperate and tropical habitats and generally infect both sexes and all ages, although the age and sex of those infected are frequently influenced by the possibility of occupational exposure.
Abstract: Twelve distinct viruses associated with hemorrhagic fever in humans are classified among four families: Arenaviridae, which includes Lassa, Junin, and Machupo viruses; Bunyaviridae, which includes Rift Valley fever, Crimean-Congo hemorrhagic fever, and Hantaan viruses; Filoviridae, which includes Marburg and Ebola viruses; and Flaviviridae, which includes yellow fever, dengue, Kyasanur Forest disease, and Omsk viruses. Most hemorrhagic fever viruses are zoonoses, with the possible exception of the four dengue viruses, which may continually circulate among humans. Hemorrhagic fever viruses are found in both temperate and tropical habitats and generally infect both sexes and all ages, although the age and sex of those infected are frequently influenced by the possibility of occupational exposure. Transmission to humans is frequently by bite of an infected tick or mosquito or via aerosol from infected rodent hosts. Aerosol and nosocomial transmission are especially important with Lassa, Junin, Machupo, Crimean-Congo hemorrhagic fever, Marburg, and Ebola viruses. Seasonality of hemorrhagic fever among humans is influenced for the most part by the dynamics of infected arthropod or vertebrate hosts. Mammals, especially rodents, appear to be important natural hosts for many hemorrhagic fever viruses. The transmission cycle for each hemorrhagic fever virus is distinct and is dependent upon the characteristics of the primary vector species and the possibility for its contact with humans.

Journal ArticleDOI
TL;DR: An immunoglobulin G enzyme-linked immunosorbent assay (IgG-ELISA) for the detection of dengue antibodies is described and compared to the haemagglutination inhibition test (HI).
Abstract: An immunoglobulin G enzyme-linked immunosorbent assay (IgG-ELISA) for the detection of dengue antibodies is described and compared to the haemagglutination inhibition test (HI). The sensitivity, specificity and agreement rate between the 2 techniques were good. The coefficients of correlation between IgG-ELISA and HI results, using dengue 1-4 antigens, were highly significant (P less than 0.001 for either antigen). IgG-ELISA was rapid, and easy to perform and suitable for large-scale studies. Between April and June 1987, a baseline serosurvey of the prevalence of dengue antibodies in age-stratified samples of children was carried out in Tahiti using IgG-ELISA. 327 children were tested against each dengue serotype. There was no significant difference between sex. Overall rates ranged from 7.4% in children under 5 years to 83.1% in those aged 15-19 years. Dengue 4 being the only serotype involved since 1979, specific responses to dengue 4 were found in higher proportion among children under 8 years old, while the IgG-ELISA responses were more widely reactive among children aged above 8 years (P less than 0.001). The acquisition rate of dengue 4 antibodies was 2.95% on average per year in children under 8 years of age.

01 Apr 1989
TL;DR: It is confirmed that the epidemic hemorrhagic fever in the people's Republic of China and the Far Eastern hemorrhagic nephroso-nephritis in the Soviet Union are caused by the same virus and the HFRS in European Russian and the Balkan countries and nephropathia epidemica in Scandinavia is caused by Puumala virus, an antigenically related Bunyavirus that is distinguishable serologically from Hantaan virus.
Abstract: : Studies have confirmed that the epidemic hemorrhagic fever in the people's Republic of China and the Far Eastern hemorrhagic nephroso-nephritis in the Soviet Union are caused by the same virus and the HFRS in European Russian and the Balkan countries and nephropathia epidemica in Scandinavia are caused by Puumala virus, an antigenically related Bunyavirus that is distinguishable serologically from Hantaan virus. The nephropathia epidemica antigen has been detected and the virus has been isolated from the lungs of the reservoir bank voles (Clethrionomys glareolus). In addition, serologic surveys of patients in Sweden, Finland, Hungary, Yugoslavia, and European Russia have shown that both the Hantaan and Puumala serotypes are circulating in these areas. The availability of Hantaan virus antigen has further permitted the diagnosis of urban cases throughout Korea, China, and Japan of a disease, transmitted to man from urban commensal rats (Ratus norvegicus and Rattus rattus), which is characterized by mild nephropathy with minimal shock or hemorrhagic diathesis or by only flu-like symptoms with albuminuria. Thus, Hantaan and related viruses cause an acute viral nephropathy across much of the Eurasian landmass in the form of a hemorrhagic disease of great clinical severity. Mortality rates range from 5% to more than 20% in East Asia. Lower mortality rates are found in nephropathia epidemica, a much milder form of non-hemorrhagic nephropathy in Scandinavia.

Journal ArticleDOI
TL;DR: Antibodies against Chikungunya virus were the most prevalent, followed by flavivirus antibodies (16%), which were probably due mainly to West Nile virus, and no evidence of yellow fever or dengue virus circulation was observed.
Abstract: Sera collected in May 1984 from 132 adult residents of Karamoja district, Uganda, were examined by haemagglutination inhibition tests for antibodies against selected arboviruses, namely Chikungunya and Semliki Forest alphaviruses (Togaviridae); dengue type 2, Wesselsbron, West Nile, yellow fever and Zika flaviviruses (Flaviviridae); Bunyamwera, Ilesha and Tahyna bunyaviruses (Bunyaviridae); and Sicilian sandfly fever phlebovirus (Bunyaviridae); and by immunofluorescence tests against certain haemorrhagic fever viruses, Lassa fever arenavirus (Arenaviridae), Ebola-Sudan, Ebola-Zaire and Marburg filoviruses (Filoviridae), Crimean-Congo haemorrhagic fever nairovirus and Rift Valley fever phlebovirus (Bunyaviridae). Antibodies against Chikungunya virus were the most prevalent (47%), followed by flavivirus antibodies (16%), which were probably due mainly to West Nile virus. No evidence of yellow fever or dengue virus circulation was observed. A few individuals had antibodies against Crimean-Congo haemorrhagic fever, Lassa, Ebola and Marburg viruses, suggesting that these viruses all circulate in the area.

Journal Article
TL;DR: There was an increase in platelet secretory activity of BTG and PF4 along with an impairment of the platelet aggregation during acute phase of DHF, which lasted only 3-4 days after shock or subsidence of fever.
Abstract: Platelet aggregation, plasma betathromboglobulin (BTG) and platelet factor 4 (PF4) were studied in 35 children with dengue hemorrhagic fever. The suppression of platelet aggregation was demonstrated during acute phase of DHF in both shock and non-shock patients. Simultaneous with abnormal platelet aggregation, there was increased release of BTG and PF4 from platelets into plasma during the acute phase which lasted only 3-4 days after shock or subsidence of fever. Acute phase plasma during DHF infection was also shown to have a stimulatory effect on the aggregation of autologous platelets. In this study we showed that there was an increase in platelet secretory activity of BTG and PF4 along with an impairment of the platelet aggregation during acute phase of DHF.

Journal ArticleDOI
TL;DR: A severe epidemic of dengue hemorrhagic fever in Nakhon Ratchasima, Thailand in August of 1987 prompted a field investigation, in which conventional control measures were only moderately effective.
Abstract: A severe epidemic of dengue hemorrhagic fever (DHF) in Nakhon Ratchasima, Thailand in August of 1987 prompted a field investigation. DHF rates of 0.4–6.5 cases per 1,000 residents in subdistricts and 2–15 cases per 1,000 residents in 10 villages investigated were reported. Epidemics peaked in neighboring villages at different times; in June and July, and in August before the rainy season began late in the month. In 4 primary schools representing 6 villages, sera from groups of randomly selected children were tested for dengue IgM with the antibody capture ELISA test. Rates of recent dengue infection were 10–65% in the schools and correlated closely with reported rates of DHF. In an effort to control vectors, malathion fog and temephos (1% abate sand granules) were applied. Villagers were educated in prevention and were urged to cover water receptacles. The percentage of houses with larvae dropped from 67 to 20, the percentage of containers with larvae decreased from 30 to 5, and the number of containers with larvae per 100 households decreased from 221 to 33. This was a serious epidemic in which conventional control measures were only moderately effective.

Journal ArticleDOI
TL;DR: Use of a mouse monoclonal antibody enabled identification of two regions (50AKQPATLR57 and127GKVVLPEN134) and possibly a third (349GRLITVNP356) in the envelope protein of dengue 2 likely to be involved in haemagglutination inhibition and virus neutralization in vitro.
Abstract: Antisera from dengue patients and dengue virus infected rabbits recognized octapeptides corresponding to linear amino acid sequences in the envelope protein of dengue 2 (Jamaica 1409). Although no peptide was recognized by sera from all dengue infected hosts, two peptides (216LPLPWLPG223 and448FSGVSWTM455) were recognized by sera from all dengue 2 infected rabbits. One of these448FSGVSWTM455 was also recognized by sera from both the dengue 2 patients tested. No peptides were identified which reacted exclusively with all dengue 2 infected animals. Use of a mouse monoclonal antibody (1B7) enabled identification of two regions (50AKQPATLR57 and127GKVVLPEN134) and possibly a third (349GRLITVNP356) in the envelope protein of dengue 2 likely to be involved in haemagglutination inhibition and virus neutralization in vitro.

Journal ArticleDOI
01 Oct 1989-Virology
TL;DR: Constancy in the microevolutionary rate and genetic variability suggests that a balance of genetic drift and natural selection acting on the viral population did not significantly change throughout the 25-year period.

Journal ArticleDOI
TL;DR: The weight of the evidence suggests that the reemergence of d Dengue in China resulted from the introduction of the infection by travelers and refugees from areas of Asia where dengue is endemic.
Abstract: In 1978, dengue was reported in China for the first time in 32 years. Since then, epidemics involving hundreds of thousands of people have occurred in Guangdong and Guangxi provinces and on Hainan Island. These epidemics were caused by all four types of dengue virus. Aedes aegypti was the vector in coastal areas, while Aedes albopictus was the vector in inland regions. During these epidemics, case rates were very high (greater than 50%) in some areas. Case-fatality rates were generally less than 0.1% except during the 1986 outbreak on Hainan Island, when the rate was 0.25%. Hemorrhagic disease occurred in both children and adults. On Hainan Island, hemorrhagic disease was more than three times as common in the 1986 outbreak as in the 1980 outbreak; the 1980 outbreak was caused by dengue virus type 3 and the 1986 outbreak by dengue virus type 2. The weight of the evidence suggests that the reemergence of dengue in China resulted from the introduction of the infection by travelers and refugees from areas of Asia where dengue is endemic.

Journal ArticleDOI
Leon Rosen1
TL;DR: It has been proposed that the disease may be more severe if an infection with one dengue serotype follows infection with another serotype, but the present reviewer does not find the data convincing.
Abstract: Dengue can be caused by any one of four viruses that are antigenically related but not cross-protective. It has been proposed that the disease may be more severe if an infection with one dengue serotype follows infection with another serotype. Both experimental and epidemiologic data have been cited to substantiate this concept, but the present reviewer does not find the data convincing. The issue is of practical importance because of its relevance to the use of dengue vaccines now under development. It is impossible to prove that clinical manifestations of dengue are not exacerbated by sequential infections. Negative findings can always be countered by arguments that exacerbation occurs only with certain serotypes, only with certain strains of those serotypes, or only when infections occur at critical intervals. Interested persons can examine the relevant data and decide whether the concept of disease exacerbation following sequential dengue infections is myth or reality.

Journal ArticleDOI
TL;DR: It is suggested that leukopenia in dengue fever may be caused by virus-induced destruction or inhibition of myeloid progenitor cells and thrombocytopenia may result from by destruction of peripheral platelet or bone marrow megakaryocytes by viruses which consequently reduce the platelet production.
Abstract: Fifty patients with dengue fever from Sept. 1987 to Jan. 1988 were studied for hematological features. The lowest blood counts values throughout the course of illness were Hb:13.2±1.9 gm/dl, WBC: (2.77±1.63)×103 /mm3 , Plaatelet: (8.7±5.5)×104 /mm3 . Leukopenia (WBC<4000/mm3) was present in 38 (76%) of the cases and thrombocytopenia (platelet<10×104 /mm3) in 27 (54%) of the cases. Leukocytes reached nadir (1000-2000/ mm3) at the 5th-6th day after fever onset, thrombocytes reached nadir (2.0-5.0×104 /mm3) at the 5th-7th day after fever onset. Bone marrow studies showed mild hypocellularity in the acute stage (<1 week) and normal cellularity in the convalescent stage (>1 week). Megakaryocytes increased with various stages of maturation of megakaryocytes appearing in a majority of patients. Nuclear vacuolization of megakaryocytes could also be found. Bone marrow CFU-GM when performed within one week of illness showed no growth or low colony count, and was nearly normal after one week of fever onset. This study may suggest that leucopenia in dengue fever may be caused by virus-induced destruction or inhibition of myeloid progenitor cells. Thrombocytopenia may result from by destruction of peripheral platelet or bone marrow megakaryocytes by viruses which consequently reduce the platelet production.


Journal ArticleDOI
TL;DR: It is demonstrated that lymphocytes from mice immunized with dengue 4 virus proliferate in response to a combination of denge 4 virus C, pre-M, E, NS1, and NS2a proteins expressed in Sf9 cells with a recombinant baculovirus, and, to a lesser extent, to the dengu 4 virus E protein alone.
Abstract: Definition of the T-lymphocyte responses to dengue viruses should aid in the development of safe and effective vaccines and help to explain the pathophysiology of dengue hemorrhagic fever and dengue shock syndrome. In this study, we demonstrated that dengue virus-specific T lymphocytes were detected in spleen cells from dengue virus-immune mice using an in vitro proliferation assay. Following immunization with a single dose of infectious dengue virus, murine lymphocytes showed increased proliferation when incubated in the presence of viral antigens of the same serotype but not in the presence of control antigens. Depletion experiments with antibody and complement showed that the population of responding cells expressed the Thy1+ L3T4+ Lyt2- phenotype. This indicates that the predominant proliferating cells are T lymphocytes of the helper-inducer phenotype. Dengue virus-specific memory lymphocyte responses were detectable for at least 22 weeks after immunization. The response to primary infection was primarily serotype specific, with some serotype cross-reactivity present at a low level. We demonstrated that lymphocytes from mice immunized with dengue 4 virus proliferate in response to a combination of dengue 4 virus C, pre-M, E, NS1, and NS2a proteins expressed in Sf9 cells with a recombinant baculovirus, and, to a lesser extent, to the dengue 4 virus E protein alone.

Journal ArticleDOI
TL;DR: The usefulness of IgM antibody capture enzyme-linked immunosorbent assay (ELISA-IgM) for the diagnosis of dengue was studied using several groups of sera and a positive response was obtained for the homologous antigen in all cases.

Journal ArticleDOI
TL;DR: Data suggested that dengue virus may have been the cause of the epidemic among the Dam Camp refugees, a refugee camp near Hargeysa in Somalia, during 1985, 1986, and 1987.
Abstract: Epidemics of a malaria-like illness affected several thousand residents of the Dam Camp, a refugee camp near Hargeysa in Somalia, during 1985, 1986, and 1987. The disease was characterized by fever, chills, sweats, headache, back and joint pains for as long as 10 days in some patients. Blood smears from acutely ill patients were negative for malaria. Of 28 acute and 10 convalescent sera tested by the indirect fluorescent antibody (IFA) and by the hemagglutination inhibition (HI) tests, all were negative for antibody to Rift Valley fever, Crimean-Congo hemorrhagic fever, Sindbis, Chikungunya, yellow fever, and Zika viruses. However, antibody reactive to dengue 2 virus was detected by the IFA test in 39% (15/38), and 11 of 29 (38%) of the same sera were antibody positive by the HI test. Also, IgG antibody reactive to dengue 2 was demonstrated in 60% (17/28) of the same sera by the enzyme immunoassay (EIA), and 14% (4/28) were positive for IgM antibody. Of ten patients for which acute and convalescent sera were available, two developed four fold or greater rises in antibody titer evidencing infection. These data suggested that dengue virus may have been the cause of the epidemic among the Dam Camp refugees.

Journal Article
TL;DR: It is predicted that there may be yet another outbreak in the following year effecting those susceptible when the rainfall season comes, and only a prior month of precipitation can explain the outbreak of dengue by stepwise multiple regression.
Abstract: Dengue fever, a tropical communicable disease, is caused by an infectious viral disease. It is also known as break bone fever. There have been a number of epidemics over the last century in Taiwan. Following an islandwide epidemic in 1942, dengue fever had not been presented on the island for about forty years. In 1981, an outbreak of dengue occurred in Liuchiu Hsiang, a small off-shore island of Pingtung county. The estimated attack rate was 80%. DEN-2 was isolated during that outbreak. Another occurrence occurred in the fall of 1987 in the southern part of Taiwan. The accumulated reported cases reached 1,387 at the end of that year. A majority of cases were reported in the Sanmin district of Kaohsiung city. The reported cumulative incidence was 0.2% in Sanmin. However, according to one survey, the attack rate in that area was 2.9%. DEN-1 was most commonly isolated but DEN-2 was also found in five cases. The latest outbreak took place in 1988. The estimation of reported cases exceeded 10,000 at the end of November, 1988. Two cases of dengue haemorrhagic fever were confirmed. More than fifty percent of the report case came from Kaohsiung city. The reported cumulative incidence rate was 0.5% in that area. Another survey reported that the adult attack rate exceeded 5% in the same area. It is estimated that the number of patients with mild symptoms and those without any symptoms would be a few times more than the number of those actually reported. However, a large space of herd immunity for susceptible hosts has remained. DEN-1 was isolated from all of the reported cases except two in which DEN-4 were isolated. Among the various variables which would effect the proliferation of disease, such as Aedes aegypti density, precipitation, and temperature, only a prior month of precipitation can explain the outbreak of dengue by stepwise multiple regression. Besides this, there was also a higher relative risk due to a higher population density with a trend correlation. Because of the ineffectiveness of the present control program, it is predicted that there may be yet another outbreak in the following year effecting those susceptible when the rainfall season comes.

Fontenille D1
01 Jan 1989
TL;DR: The risk of potential introduction and amplification of various arboviruses (dengue, yellow fever, japanese encephalitis, Sindbis and Chikungunya) is very high for dengue due to the presence of susceptible mosquitoes strains while the virus circulates in East Africa and in the Indian Ocean area.
Abstract: Some arboviruses are highly pathogenic for Men or animals, Arboviruses epidemiological patterns in Madagascar were determined by entomological, serological, and virological surveys. We listed potentials arboviruses vectors in Madagascar. Entomological results generated by us during five years, as well as prior to, are shown. We caught more than 150,000 hematophagous arthropods, belonging to 107 species at least. 3 of these species were new. 4183 inoculation pools were done. We studied serologically (by HI test) samples collected from 563 animals and 626 Men. Our data, in agreement with others collected from 1965 to 1982, demonstrate that arboviruses circulate in the whole island. Positive reactions were obtained mainly with Flavivirus, in particular with West-Nile. Nine various arboviruses, including dengue-2 virus isolated from an individual having travelled to La Reunion, have been isolated. Dakar-Bat and Mengo virus have been observed. We studied transmission cycles of the following viruses: Babanki, West-Nile, Rift Valley Fever, Crimean-Congo Hemorrhagic Fever, MMP 158, Ngari, Perinet and Andasibe; the last 2 being endemic. In relation to Madagascar biogeographic characteristics (long-term isolation, scarce communications, high endemicity, and low vertebrate density), we evaluated the risk of potential introduction and amplification of various arboviruses (dengue, yellow fever, japanese encephalitis, Sindbis and Chikungunya). The risk is very high for dengue due to the presence of susceptible mosquitoes strains while the virus circulates in East Africa and in the Indian Ocean area. This risk seems to be very low for yellow fever, and intermediate for other arboviruses.

Journal ArticleDOI
TL;DR: The detection of immunoglobulin (Ig)G and IgM antibodies to dengue 1 virus was studied by a simple enzyme immunoassay, EIA-ICC, and the antibodies were cross-reactive among the flaviviruses.
Abstract: The detection of immunoglobulin (Ig)G and IgM antibodies to dengue 1 virus was studied by a simple enzyme immunoassay, in which infected cultured cells infected with dengue virus were used as antigen (EIA-ICC). Detection of anti-dengue 1 IgG by EIA-ICC was correlated with haemagglutination assays. EIA-ICC anti-dengue 1 IgM detection was less sensitive than IgM capture enzyme-linked immunosorbent assay. IgG and IgM responses in dengue 1 infection were studied by EIA-ICC, using sera collected at different intervals after onset of illness: IgM and IgG appeared on the 4th day of disease; the highest IgM mean titres were detected on the 7th day and IgM was not detected in sera obtained after the 60th day; the highest mean titres of anti-dengue 1 IgG were seen in sera obtained between 22 and 30 d after onset of illness. EIA-ICCs for 6 flaviviruses and 1 alphavirus were conducted with sera from patients infected with dengue 1, and primary and secondary infections of other flaviviruses. The results showed that anti-dengue 1 IgG detection was sensitive, and the antibodies were cross-reactive among the flaviviruses. Anti-dengue 1 IgM detected in dengue 1 patients was mostly type specific. The pattern of secondary dengue infection, i.e. the presence of IgG and a low titre or absence of IgM antibodies, was observed in the sera of 6 patients obtained in the first week after onset of illness. EIA-ICC is useful for dengue diagnosis, surveillance and sero-epidemiological studies.