Showing papers on "Dengue virus published in 1987"

Protection of Mice Against Dengue 2 Virus Encephalitis by Immunization with the Dengue 2 Virus Non-structural Glycoprotein NS1

Abstract: Summary Immunization of mice with the dengue 2 virus (DEN 2)-specified non-structural protein NS1 provided significant protection against intracerebral challenge with the virus in the absence of detectable neutralizing or other anti-virion antibody. NS1, purified from lysates of infected Vero cells by immunoaffinity chromatography, expressed an antigenic site(s) common to each of the four DEN serotypes, and hyperimmunization of rabbits with NS1 stimulated production of complement-fixing (CF) antibody with broad DEN serotype specificity. However, cross-protection was not observed: mice immunized with DEN 2 NS1 developed little or no heterologous CF antibody and were not protected against challenge with neurovirulent DEN 1. Induction of a protective immune response by NS1 suggests that it be considered for incorporation into possible synthetic or recombinant DNA DEN vaccines.

Immunization with a live attenuated dengue-2-virus candidate vaccine (16681-PDK 53): clinical, immunological and biological responses in adult volunteers.

Abstract: A live dengue-2 (DEN-2) candidate vaccine (strain 16681-PDK 53), attenuated by passage in primary dog kidney cells, was tested in ten adult volunteers for evaluation of the safety, infectivity and immunogenicity of a dose of 1.9-2.7 x 10(4) plaque-forming units. Five of the volunteers were nonimmune to either dengue or Japanese encephalitis (JE) viruses; the other five were nonimmune to dengue but immune to JE. After receiving 1.0 ml of the vaccine subcutaneously, all ten volunteers developed neutralizing antibodies to DEN-2 which were maintained for at least one and a half years. None of the subjects developed abnormal signs or symptoms and the results of clinical chemistry investigations were within normal range throughout the 21 days of observation after the immunization. Virus isolated from one viraemic volunteer retained the small-plaque and temperature-sensitive growth characteristics of the vaccine virus in vitro. Further testing of this candidate vaccine in humans is indicated.

Why dengue haemorrhagic fever in Cuba? 2. An integral analysis

Abstract: The epidemiological factors present in Cuba in 1981, when the dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS) epidemic occurred, were exceptional when compared to those of other countries in the region. Evidence is presented which demonstrates that virulence of the circulating strain is an important element in the analysis of an epidemic. Although the two current hypotheses to explain the occurrence of DHF/DSS epidemics are valid in well defined but different epidemiological situations, neither Halstead's hypothesis of secondary-type infection or Rosen's hypothesis of the role played by the virulence of the circulating strain can explain all cases. An integrated, multifactorial and unifying hypothesis is presented, which could be applied in different epidemiological situations. It is based mainly on an in-depth analysis of the literature and of the Cuban experience.

Dengue Hemorrhagic Fever: Diagnosis, Treatment and Control: by the World Health Organization vii + 58 pages, illustrated, World Health Organization, 1211 Geneva 27, Switzerland. 1986. $7.80

Abstract: This paperbound booklet is the second revision of a manual issued in 1975. It is relatively expensive for those countries where dengue (DEN), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS) exist or are feared. Chapter 1, General Considerations, gives historical perspective and an idea of the dimensions of the problem. The orientation is obviously Southeast Asia, and one wonders why Australia is not mentioned in “other countries at risk.” It should be noted that the existence of DEN in West Africa was not reported until Carey and Causey in 1970 signalled its presence determined by virus isolation from children seen at a fever clinic at the University Hospital in Ibadan. Dengue virus(es) have since been isolated in several West African countries; DHF/DSS has not been reported. In subsection “Pathology” it could be mentioned that the virus is rarely isolated from blood or organs of DHF/DSS patients unless special isolation techniques are used.

Sexual transmission of dengue viruses by Aedes albopictus.

Abstract: Male Aedes albopictus experimentally infected with dengue virus types 1, 2, 3, or 4 transmitted their infection sexually to female Ae. albopictus. Such transmission was enhanced if the females had taken a bloodmeal 2 to 7 days prior to mating. Male Ae. albopictus also transmitted dengue virus vertically to their F1 progeny. Infected progeny were found among those derived from eggs laid greater than or equal to 73 hr after mating but not among those derived from eggs laid prior to that time. This suggests that virus probably was not transmitted directly to ova but, rather, underwent prior replication in the female genital tract. Female Ae. albopictus experimentally infected with dengue type 1 virus did not transmit their infection sexually to males. This finding supports the hypothesis that male mosquitoes naturally infected with dengue virus acquired their infection vertically.

Expression of dengue virus structural proteins and nonstructural protein NS1 by a recombinant vaccinia virus.

Abstract: A recombinant vaccinia virus containing cloned DNA sequences coding for the three structural proteins and nonstructural proteins NS1 and NS2a of dengue type 4 virus was constructed. Infection of CV-1 cells with this recombinant virus produced dengue virus structural proteins as well as the nonstructural protein NS1. These proteins were precipitated by specific antisera and exhibited the same molecular size and glycosylation patterns as authentic dengue virus proteins. Infection of cotton rats with the recombinant virus induced NS1 antibodies in 1 of 11 animals. However, an immune response to the PreM and E glycoproteins was not detected. A reduced level of gene expression was probably the reason for the limited serologic response to these dengue virus antigens.

Lack of attenuation of a candidate dengue 1 vaccine (45AZ5) in human volunteers.

Abstract: A dengue type 1, candidate live virus vaccine (45AZ5) was prepared by serial virus passage in fetal rhesus lung cells. Infected cells were treated with a mutagen, 5-azacytidine, to increase the likelihood of producing attenuated variants. The vaccine strain was selected by cloning virus that produced only small plaques in vitro and showed reduced replication at high temperatures (temperature sensitivity). Although other candidate live dengue virus vaccines selected for similar growth characteristics have been attenuated for humans, two recipients of the 45AZ5 virus developed unmodified acute dengue fever. Viremia was observed within 24 hr of inoculation and lasted 12 to 19 days. Virus isolates from the blood produced large plaques in cell culture and showed diminished temperature sensitivity. The 45AZ5 virus is unacceptable as a vaccine candidate. This experience points out the uncertain relationship between in vitro viral growth characteristics and virulence factors for humans.

Vector competence of Aedes albopictus from Houston, Texas, for dengue serotypes 1 to 4, yellow fever and Ross River viruses.

Abstract: A combination of virus infection and transmission experiments showed that a Houston, Texas strain of Aedes albopictus is a competent vector for dengue (DEN), yellow fever (YF) and Ross River (RR) viruses. However, at 14 days incubation, DEN virus infection rates in a Puerto Rican strain of Aedes aegypti were significantly higher for each of the four DEN serotypes, except DEN-1, than in Houston Ae. albopictus fed simultaneously on the same virus suspensions. The degree of correlation between disseminated DEN infection rates in Houston Ae. albopictus and transmission to an in vitro system ranged from 42 to 88% for the four DEN serotypes. No significant difference was noted in YF virus infection rates or transmission rates in the two mosquito species fed on the same virus suspensions and incubated for the same time period. Also, RR virus infection and transmission rates in Houston and Hawaiian strains of Ae. albopictus were generally comparable.

Characterization of protease cleavage sites involved in the formation of the envelope glycoprotein and three non-structural proteins of dengue virus type 2, New Guinea C strain.

Abstract: Summary Amino terminal sequences of the envelope protein E and the three largest nonstructural proteins NS1, NS3, and NS5 of the New Guinea C strain of dengue virus type 2 (DEN-2) were obtained by nucleotide and protein sequencing. Clones were prepared containing cDNA of DEN-2 virus in the plasmid pUC8. The nucleotide sequences of viral cDNA inserts were determined and the cDNA of each clone positioned on the flavivirus genomic map by comparison of the deduced amino acid sequence with that of yellow fever virus. Radiolabelled E, NS1, NS3 and NS5 were purified by lectin affinity chromatography and preparative gel electrophoresis. Purified proteins were subsequently analysed by Edman degradation to establish the origins of the amino termini of these proteins in the deduced DEN-2 amino acid sequence. Thus the amino acid sequences surrounding the likely proteolytic cleavage sites used in the formation of these four proteins were determined. Of particular interest was the sequence containing the amino terminus of NS3, namely Lys-Lys-Gln-Arg-Ala-Gly where Ala is the first amino acid of NS3. Cleavage following one basic residue in the flavivirus polyprotein has not been reported previously.

Epidemiological aspects of an outbreak of dengue fever/dengue haemorrhagic fever in Singapore.

Abstract: A nation-wide outbreak of 260 cases of DF/DHF with 1 death occurred in Singapore from Apr-Sept 1986. The outbreak originated from 3 separate foci of transmission at the western, south-eastern and north-eastern parts of the island and then spread to other dengue receptive urban and suburban areas. The morbidity rate was highest in young male Chinese adults between 15 and 24 years of age. The outbreak was rapidly brought under control through destruction of adult Aedes mosquitoes, surveys and source reduction of larval breeding habitats, health education and to a certain extent law enforcement. The Aedes population was high in the main foci of transmission although the overall house index was only 1.1. Other factors which could have precipitated the outbreak included waning herd immunity of the human population and continuous introduction of dengue virus into the country.

Three possible triggers to induce thrombocytopenia in dengue virus infection.

Abstract: Changes in platelet count by dengue virus-platelet interaction and the participation of anti-DV antibody to such changes were studied in vitro with the aim to investigate a mechanism of how the DV causes prominent thrombocytopenia characteristically seen in DHF. The results obtained showed that: (1) DV antigen attached to human platelets without immune-mediated reaction, (2) a decrease in platelet count was more markedly demonstrated by the binding of anti-DV antibody on the DV antigen associated with platelets than by the binding of the antigen-antibody complex on platelets, (3) a modulation of endothelial cell by the infection of DV to the cell was suggested as one of the causes of the thrombocytopenia.

Vertical transmission of dengue viruses by mosquitoes of the Aedes scutellaris group.

Abstract: Seventeen strains of mosquitoes belonging to 12 species in the Aedes scutellaris subgroup were tested for an ability to transmit one or more dengue virus serotype(s) vertically. Strains of virus employed for dengue types 1, 2, 3, and 4 were from Fiji, Bangkok, Burma, and Medan, respectively. After parental females were infected by intrathoracic inoculation, F1 larval and pupal progeny were tested for the presence of virus by inoculating aliquots of triturated suspensions into Toxorhynchites amboinensis mosquitoes. Dengue type 1 was transmitted vertically by 11 strains of mosquitoes representing 8 species with the highest filial infection rates observed for Ae. cooki (1.2%). Vertical transmission of the other dengue virus serotypes was observed for fewer species of mosquitoes, however the filial infection rates of those demonstrating vertical transmission were between 1%-2% for types 2 and 3, and about 0.5% for type 4. Tests with the progeny of individual Ae. cooki and Ae. polynesiensis infected with dengue virus types 1 and 3, respectively, showed that approximately greater than or equal to 50% of the parental females transmitted virus to their progeny. Highest filial infection rates were 6.7% for Ae. cooki and 4.6% for Ae. polynesiensis.

Susceptibility of Aedes albopictus C6/36 cells to viral infection.

Abstract: The susceptibility of the C6/36 clone of Aedes albopictus monolayer cell cultures was determined with 46 prototype viruses passed through three subcultures. Viral growth was confirmed by titration of the passage material in other susceptible host systems. Nineteen viruses demonstrated good growth in C6/36 cells: coxsackievirus group A type 10 and group B types 2, 3, 4, and 5; enterovirus 69; mumps virus; poliovirus types 1 to 3; reovirus types 1 to 3; vaccinia virus; dengue virus type 2; eastern equine encephalomyelitis virus; La Crosse virus; Rocio virus; and St. Louis encephalitis virus. Ten viruses did not adapt to growth in the C6/36 cultures. Seventeen other virus strains displayed only limited growth which was primarily restricted to the initial C6/36 passage or was detected by hemagglutinin reactions without observable cell degeneration. Of the 46 viruses, 33 (72%) were capable of initiating infection with a demonstrable cytopathic effect in the initial C6/36 passage. Hemagglutination or complement fixation titers or both were obtained with dengue virus type 2, eastern equine encephalomyelitis virus, La Crosse virus, mumps virus, reovirus types 1 to 3, and Rocio, St. Louis encephalitis, and vaccinia viruses.

Induction of interferon alpha from human lymphocytes by autologous, dengue virus-infected monocytes.

Abstract: Human monocytes actively replicate dengue virus. To dissect the primary immune responses to dengue virus-infected monocytes (DV-monocytes), we analyzed the interaction between autologous DV-monocytes and the peripheral blood lymphocytes (PBL) of dengue nonimmune donors. Interferon (IFN) activity was detected when PBL were cultured with DV-monocytes. Cell contact between PBL and DV-monocytes was required for IFN production; however, MHC compatibility between PBL and monocytes was not necessary. DV-monocytes fixed with paraformaldehyde or glutaraldehyde, which produced no infectious virus, also induced high levels of IFN from PBL. The ability of DV-monocytes to induce IFN correlated with the appearance of dengue antigens. The PBL that produce IFN were characterized by FACS sorting using monoclonal and polyclonal antibodies. HLA-DR+ and T3- cells produced high titers of IFN, while HLA-DR- and T3+ cells produced very low or undetectable levels of IFN. Moderate titers of IFN were produced by cells contained in B cell fractions (surface immunoglobulin-positive, B1+, and Leu-12+), and cells contained in natural killer cell fractions (Leu-11+ and OKM1+). Therefore, IFN-producing cells are heterogeneous, and the predominant producer cells are characterized as HLA-DR+ and non-T lymphocytes. The IFN produced was characterized by RIA using mAbs to IFN-alpha and IFN-gamma. The IFN-alpha was the predominant IFN produced; in addition, a low level of IFN-gamma was also detected in some experiments. The culture fluids obtained from PBL exposed to autologous DV-monocytes, which contained high IFN activity, completely inhibited dengue virus infection of monocytes. These results suggest that IFN-alpha produced by PBL exposed to DV-monocytes may play an important role in controlling primary dengue virus infection.

Mechanism of vertical transmission of the dengue virus in mosquitoes.

Abstract: Both experimental and field data suggest that some tropical mosquito-borne flaviviruses, such as dengue and yellow fever, survive dry seasons by vertical (i.e. transgenerational) transmission in their mosquito hosts. Although vertical transmission of arboviruses in mosquitoes is considered to be transovarial in nature, observations reported here indicate that this is probably not true for dengue virus. Rather, infection of the next generation with this virus apparently takes place when the fully developed egg, enclosed in the chorion, is fertilized at the time of oviposition. In contrast to transovarial transmission, the latter mechanism permits the infection of progeny following a single maternal blood meal.

Current Research on Dengue

Abstract: Dengue is the most important arbovirus disease of humans, in terms of both morbidity and mortality (1). Since the end of World War II, the incidence of dengue disease has increased greatly. Coincident with that increase has been the emergence and spread of a severe and fatal form of the disease, dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), as a major public health problem in many areas of the tropics. Today DHF is a leading cause of hospitalization and death among children in many countries of Southeast Asia (2), and in recent years it has become increasingly important in the Pacific Islands and the Americas.

Increased Dissemination of Dengue 2 Virus in Aedes aegypti Associated with Concurrent Ingestion of Microfilariae of Brugia malayi

Abstract: : We investigated whether concurrent ingestion of dengue 2 virus and microfilariae of Brugia malayi would increase viral infection and dissemination rates in Aedes aegypti. Infection rates were similar in mosquitoes that ingested virus along or both virus and microfilariae concurrently. However, viral dissemination rates, as determined by recovery of dengue virus from both legs and bodies separately, were significantly greater in mosquitoes that ingested both agents concurrently than in those that ingested virus alone. This study confirms that vectorial capacity of a natural vector of an arbovirus may be enhanced by the concurrent ingestion of microfilariae.

Detection of Flavivirus Antibodies in Human Serum by Epitope-Blocking Immunoassay

Abstract: : Human flavivirus group-reactive, dengue complex-reactive, and encephalitis virus complex-reactive antibodies were detected using epitope-blocking immunoassays in which the binding of selected mouse monoclonal antibodies to flavivirus antigens was blocked by human serum. When late (> 6 months after illness) convalescent sera were tested, the epitope-blocking immunoassays were superior to the hemagglutination inhibition test and comparable to the plaque reduction neutralization for identifying subjects immune to dengue, to Japanese encephalitis, or both viruses. We constructed a series of assays that measure the ability of a test serum to block the binding of an enzyme-labeled monoclonal antibody to its corresponding epitope on the viral antigen. We call this test the Defined Epitope Blocking Enzyme-Linked Immunosorbent Assay, or DEB-ELISA. Keywords: Diagnosis medicine; Reprints.

Study of the distribution of antibody-dependent enhancement determinants on dengue 2 isolates using dengue 2-derived monoclonal antibodies.

Abstract: Dengue 2 (DEN-2) strains isolated from children during the 1980 metropolitan Bangkok epidemic were shown to possess antigenic homogeneity when studied for determinants mediating antibody-dependent infection enhancement using DEN-2 monoclonal antibodies. All isolates possessed multiple enhancing determinants, but those associated with mild and severe dengue syndromes could not be distinguished. Either the basis of disease severity in dengue is more complex than the mere presence or absence of virus epitopes involved in enhanced infection or enhancing epitopes have differences not detected in this system with monoclonal antibodies raised to the same serotype.

Outbreak of febrile illness due to dengue virus type 3 in Calcutta during 1983

Abstract: An epidemic of dengue fever broke out in Calcutta between July and August 1983. Persons of all age groups were affected with a preponderance of young adults. Haemorrhagic manifestations and shock were not observed. Virus was isolated from 4 acute phase sera and identified as dengue type 3 (DEN-3), the first isolation of DEN-3 virus in Calcutta. Serotesting with 9 paired blood samples established dengue infection in 7 and a flavivirus group reaction in 2. Examination of 36 single sera revealed presumptive dengue infection in 15 and a flavivirus group reaction in 17, while the remaining 4 were negative to all flavivirus antigens.

Serological survey on dengue virus infection in Singapore.

Abstract: A serological study on dengue infection conducted in Singapore during the period 1982 to 1984 showed that 54.4% of the healthy population between 6 months and over 50 years of age surveyed possessed no haemagglutination-inhibition antibody to dengue type 2 virus. Children below 10 years of age showed the lowest antibody prevalence and were at the greatest risk, with 96.6% susceptible to infection, whereas virtually all adults over 40 showed evidence of prior dengue infection, The geometric mean titre showed a rising trend indicating continuing acquisition of infection in the older age groups. The seropositivity rate of dengue infection of males was twice that of females. Among the 3 major ethnic groups, no significant difference in seropositivity was noted between the Malays and Indians, but the differences between Malays and Chinese and between Indians and Chinese were statistically significant. The study confirmed that the successful implementation of the nation-wide Aedes control programme is reducing endemic dengue virus transmission in the country.

Dengue virus-induced helper T cells.

Abstract: Inoculation intraveineuse de souris avec le virus de la dengue 2. Induction de la production de cellules T dans la rate. Le maximum de la production de cellules formant des anticorps est de 43% ce qui est considerablement moins que ce qui est observe dans d'autres modeles

Protection against marked plasma leakage in dengue haemorrhagic fever by infusion of carbazochrome sodium sulfonate (AC-17).

Abstract: Patients diagnosed clinically as having grade II dengue haemorrhagic fever, and confirmed serologically to have been recently infected by dengue virus were randomly assigned to two groups, to assess suppression of plasma leakage by intravenous administration of carbazochrome sodium sulfonate(AC-17). The double-blind prospective study over three successive epidemic periods included 39 patients in the placebo group, and 38 in the AC-17 group. The effects of the administration were evaluated with respect to pleural effusion of the chest X-ray films. A clear difference between the two groups was found in the numbers of patients with pleural effusion and severity of the pleural effusion thus the administration of AC-17 may be useful in eliminating the risk factors of severe bleeding and shock in dengue haemorrhagic fever.