Showing papers on "Dengue fever published in 1994"
TL;DR: At the root of the emergence of dengue as a major health problem are changes in human demography and behavior, leading to unchecked populations of and increased exposure to the principal domestic mosquito vector, Aedes aegypti.
Abstract: Dengue viruses are members of the Flaviviridae, transmitted principally in a cycle involving humans and mosquito vectors. In the last 20 years the incidence of dengue fever epidemics has increased and hyperendemic transmission has been established over a geographically expanding area. A severe form, dengue hemorrhagic fever (DHF), is an immunopathologic disease occurring in persons who experience sequential dengue infections. The risk of sequential infections, and consequently the incidence of DHF, has risen dramatically, first in Asia and now in the Americas. At the root of the emergence of dengue as a major health problem are changes in human demography and behavior, leading to unchecked populations of and increased exposure to the principal domestic mosquito vector, Aedes aegypti. Virus-specified factors also influence the epidemiology of dengue. Speculations on future events in the epidemiology, evolution, and biological expression of dengue are presented.
784 citations
TL;DR: Evidence suggests that ADE reflects immunologic processes that occur in vivo, and more data are urgently needed on the mechanisms and determinants of ADE and on its alleged role in disease pathogenesis and in vaccine-associated phenomena.
Abstract: Antibody-dependent enhancement of infection (ADE) is an in vitro serological phenomenon--or a group of phenomena--in which viral infection of susceptible cells is modified by the addition of virus-reactive antibody. Evidence suggests that ADE reflects immunologic processes that occur in vivo. Various severe and even fatal viral conditions of humans and animals, including dengue shock syndrome, the "early-death phenomenon" in experimental infections of immune animals, and other vaccine- and immunoglobulin-modified conditions, have been attributed to ADE by some researchers. ADE has caused great concern in relation to the development of vaccines against dengue virus and human immunodeficiency virus. More data are urgently needed on the mechanisms and determinants of ADE and on its alleged role in disease pathogenesis and in vaccine-associated phenomena.
308 citations
TL;DR: The occurrence of these factors and the expanding geographic distribution of dengue hemorrhagic fever in the past 15 years have made it necessary to re-evaluate currently recommended methods for prevention and control and the result has been increasing emphasis on the development of effective sustainable Aedes aegypti control programs based on source reduction using community participation.
Abstract: Dengue viruses are maintained in endemic transmission cycles in tropical urban areas where epidemics periodically occur. Until about 30 years ago, there were long intervals (10-40 years) between epidemics but they are now occurring in many areas at 3-5-year intervals. These epidemics are most likely caused by virus strains with different epidemic potential. Accompanying this increased frequency in epidemic activity has been a change in the disease pattern with cases of the severe form of dengue (dengue hemorrhagic fever) becoming much more common. The occurrence of these factors and the expanding geographic distribution of dengue hemorrhagic fever in the past 15 years have made it necessary to re-evaluate currently recommended methods for prevention and control. The result has been increasing emphasis on the development of effective sustainable Aedes aegypti control programs based on source reduction using community participation. A brief overview of global programs using this approach is presented with emphasis on the Puerto Rican program, one of the earliest developed.
123 citations
TL;DR: The results support the previous studies on the design of flavivirus-vaccinia vaccine candidates by showing the importance of co-expressing prM and E in order to induce the synthesis of extracellular E and to elicit NEUT and HAI antibodies.
108 citations
TL;DR: In this review, the complex interplay of virus, host, vector, environment and weather in the ecology of yellow fever and dengue are explored.
104 citations
TL;DR: It is hypothesize that the rapid release of cytokines and chemical mediators caused by T cell activation and by CTL-mediated lysis of dengue virus-infected monocytes triggers the plasma leakage and hemorrhage that occurs in DHF.
Abstract: Dengue virus infections are a major cause of morbidity and mortality in tropical and subtropical areas of the world. The immunopathological mechanisms that result in severe complications of dengue virus infection, i.e. dengue hemorrhagic fever (DHF), are important to determine. Primary dengue virus infections induce serotype-specific and serotype-cross-reactive, CD4+ and CD8+ memory cytotoxic T lymphocytes (CTL). In secondary infections with a virus of a different serotype from that which caused primary infections, the presence of cross-reactive non-neutralizing antibodies results in an increased number of infected monocytes by dengue virus — antibody complexes. This in turn results in marked activation of serotype cross-reactive CD4+ and CD8+ memory CTL. We hypothesize that the rapid release of cytokines and chemical mediators caused by T cell activation and by CTL-mediated lysis of dengue virus-infected monocytes triggers the plasma leakage and hemorrhage that occurs in DHF.
104 citations
TL;DR: A Thai woman with a febrile illness was delivered of a healthy infant by cesarean section and the infant developed marked thrombocytopenia, and it is believed to be the first report of vertical transmission of dengue in humans.
Abstract: A Thai woman with a febrile illness was delivered of a healthy infant by cesarean section The etiology of her 2-day fever was unknown at the time of surgery; results of serology performed later established a diagnosis of dengue infection Postoperative hemostatic monitoring was not performed She experienced massive and prolonged (8 days) wound hemorrhage that necessitated multiple transfusions of blood, platelets, and frozen plasma The newborn became febrile on his 6th day of life Dengue virus type 2 was isolated from his serum Although the infant developed marked thrombocytopenia, his illness was brief and uncomplicated This report emphasizes the hazards of surgical intervention in patients with acute dengue infection We also believe it to be the first report of vertical transmission of dengue in humans
95 citations
TL;DR: Because passage level PDK-20 may be suitable for healthy adults at high risk of dengue fever, additional clinical trials of this strain are warranted.
Abstract: A dengue-1 candidate vaccine (45AZ5), previously found to be underattenuated in 2 volunteers, was further attenuated by passage in primary dog kidney (PDK) cell cultures. New candidate vaccines prepared from three levels of PDK-passaged virus, PDK-10, PDK-20, and PDK-27, were each injected into 9 or 10 volunteers. There was a significant, progressive decline in viremia, clinical illness, and hematologic changes from low to high PDK cell passage level. PDK-20 infected all 10 vaccinees and induced viremia in 5, transient fever in 3, symptoms that resulted in curtailed activities for or = 1 year in 5 of 8 vaccinees tested. Progressive passage in PDK cell culture progressively attenuates vaccine candidate strain 45AZ5 for humans. Because passage level PDK-20 may be suitable for healthy adults at high risk of dengue fever, additional clinical trials of this strain are warranted.
93 citations
TL;DR: Spontaneous haemorrhagic manifestations occurred in 46 patients, and 23 of these had more than one kind of bleeding; petechiae and bleeding gums were the most frequent association.
Abstract: We studied 56 cases of serologically confirmed dengue haemorrhagic fever living in the metropolitan area of Niteroi and surrounding cities in the state of Rio de Janeiro, Brazil. The most frequent findings were fever and myalgia. Spontaneous haemorrhagic manifestations occurred in 46 patients, and 23 of these had more than one kind of bleeding; petechiae and bleeding gums were the most frequent association. The distribution according to the World Health Organization's criteria of severity was 6 in grade I, 23 in grade II, 24 in grade III and 3 in grade IV.
81 citations
Journal Article•
TL;DR: Several arboviruses were endemic and some of them may have caused human disease in the Northern Province of Sudan coinciding with a high population density of phlebotomine sandflies.
Abstract: An outbreak of acute febrile illness occurred during August and September 1989 in the Northern Province of Sudan coinciding with a high population density of phlebotomine sandflies. An investigation was conducted to determine whether arboviruses were associated with human illness during this outbreak. Sera were obtained from 185 febrile individuals and tested for IgG and IgM antibody to selected arboviruses by enzyme immunoassay (EIA). The prevalence of IgG antibody was 59% for West Nile (WN), 53% for Sandfly Fever Sicilian (SFS), 32% for Sandfly Fever Naples (SFN), 39% for Yellow Fever (YF), 24% for dengue-2 (DEN-2), 23% for Rift Valley Fever (RVF), 12% for Chikungunya (CHIK) and 5% for Crimean-Congo haemorrhagic Fever (CCHF) viruses. Antibody prevalences tended to increase with age for WN and YF viruses. Antibody rates were about the same for males and females for most of the viruses tested. The prevalence of IgM antibody to SFN was 24% and reciprocal IgM titre exceeded 12,800 for some individuals suggesting that this virus was the cause of recent infection. The prevalence of IgM antibody for the other viruses did not exceed 5%. The study indicated that several arboviruses were endemic and some of them may have caused human disease in the Northern Province of Sudan.
80 citations
TL;DR: This study investigated whether the candidate vaccine was efficacious in inducing dengue virus-specific CD4+ and CD8+ T cell memory after a single immunization in nonimmune recipients.
Abstract: A live attenuated dengue virus type 2 candidate vaccine (16681-PDK53) was evaluated in a phase I trial in 10 nonimmune adult volunteers. The dengue virus-specific memory T cell responses were analyzed as part of this study. Dengue virus-specific T cell proliferative responses were observed in all subjects after stimulating their peripheral blood mononuclear cells with live viruses or noninfectious viral antigens. The highest proliferative response was against dengue virus type 2, although cross-reactivity with other flaviviruses was detected to a lesser degree in some subjects. Dengue virus type 2-specific CD4+ and CD8+ cytotoxic T lymphocytes were generated in all vaccinees. This study investigated whether the candidate vaccine was efficacious in inducing dengue virus-specific CD4+ and CD8+ T cell memory after a single immunization in nonimmune recipients.
TL;DR: This review attempts to summarize recent thinking in this field and to evaluate the different systems available as potential future flavivirus vaccines in inducing protective immunity.
TL;DR: Results are consistent with the possibility that plasminogen cross-reactive antibodies play a role in the etiology of hemorrhage in dengue virus infection.
Abstract: Although dengue fever (DF) is usually self-limited, some patients experience severe and prolonged illness characterized by capillary leakage, which may progress to hypovolemic shock (dengue hemorrhagic fever/dengue shock syndrome; DHF/DSS) with hemorrhage of unknown etiology. Development of antibodies potentially cross-reactive to plasminogen has been reported in a high percentage of Thai patients with DF and DHF/DSS. Correlation between detection of plasminogen cross-reactive antibodies and hemorrhage was evaluated in 88 Tahitian children with dengue virus type 3 infection who presented with (n = 59) or without (n = 29) hemorrhage. Plasminogen cross-reactive antibodies were found in acute and convalescent sera of 33 and 11 children, respectively (56% vs. 31%, P < .05), and closely paralleled antibodies to the cross-reactive site in dengue virus E protein. Antibodies were more frequent in children with secondary than primary infections (60% vs. 32%, P < .05). Plasminogen cross-reactive antibodies did not correlate with occurrence of DHF/DSS or thrombocytopenia. These results are consistent with the possibility that plasminogen cross-reactive antibodies play a role in the etiology of hemorrhage in dengue virus infection.
22 Jul 1994
TL;DR: Dengue transmission was characterized by a cyclical pattern, with peaks in incidence occurring during months with higher temperatures and humidity (usually from September through November), and the number of laboratory-diagnosed dengue infections among travelers was small, severe and fatal disease was documented.
Abstract: PROBLEM/CONDITION Dengue is an acute, mosquito-transmitted viral disease characterized by fever, headache, arthralgia, myalgia, rash, nausea, and vomiting. The worldwide incidence of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) increased from the mid-1970s through 1992. Although dengue is not endemic to the 50 United States, it presents a risk to U.S. residents who visit dengue-endemic areas. REPORTING PERIOD COVERED 1986-1992. DESCRIPTION OF SYSTEM Dengue surveillance in the 50 United States and the U.S. Virgin Islands relies on provider-initiated reports to state health departments. State health departments then submit clinical information and serum samples to CDC for diagnostic confirmation of disease among U.S. residents who become ill during or after travel to dengue-endemic areas and among residents of the U.S. Virgin Islands. In Puerto Rico, an active, laboratory-based surveillance program receives serum specimens from ambulatory and hospitalized patients throughout the island, clinical reports on hospitalized cases, and copies of death certificates that list dengue as a cause of death. Laboratory diagnosis relies on virus isolation or serologic diagnosis of disease (i.e., IgM or IgG antibodies against dengue viruses). RESULTS In 1986, the first indigenous transmission of dengue in the United States in 6 years occurred in Texas; from the time of that incident through 1992, however, no further endemic transmission was reported. During 1986-1992, CDC processed serum samples from 788 residents of 47 states and the District of Columbia. Among these 788 residents, 157 (20%) cases of dengue were diagnosed serologically or virologically. Of the 157 patients, 71 (45%) had visited Latin America or the Caribbean; 63 (40%), Asia and the Pacific; seven (4%), Africa; and nine (6%), several continents. All four dengue virus serotypes (DEN-1, DEN-2, DEN-3, and DEN-4) were isolated from travelers to Asia and the Pacific; however, travelers to the Americas acquired infections with only DEN-1, DEN-2, or DEN-4. Even though the number of laboratory-diagnosed dengue infections among travelers was small, severe and fatal disease was documented. In the U.S. Virgin Islands and Puerto Rico, three serotypes (DEN-1, DEN-2, and DEN-4) circulated during 1986-1992. In Puerto Rico, disease transmission was characterized by a cyclical pattern, with peaks in incidence occurring during months with higher temperatures and humidity (usually from September through November). The highest incidence of laboratory-diagnosed disease (1.2 cases per 1,000 population) occurred among persons < 30 years of age; rates were similar for males and females.(ABSTRACT TRUNCATED AT 400 WORDS)
TL;DR: This outbreak was marked by the appearance of the first clinical cases of dengue hemorrhagic fever (DHF) in French Guiana, and forty cases met the World Health Organization definition of clinical DHF: 32 were grade II, seven were grade III, and one was grade IV and fatal.
Abstract: From July 1991 to October 1992, an outbreak of dengue spread into the main urban areas of French Guiana, where 90% of the country's 114,808 inhabitants live. In mid-July 1991 dengue-2 virus was identified as being responsible for most cases, while dengue-1 virus was rarely isolated and circulated at a low level. The number of dengue cases during this period was unknown because there was no clinically based dengue surveillance system. The only available data were for the number of suspected cases as indicated by the number of patients for whom blood samples were submitted to a laboratory for dengue diagnosis. Eight hundred forty-seven of the 2,948 suspected cases were diagnosed in the laboratory as dengue cases. Six fatal cases were reported. This outbreak was marked by the appearance of the first clinical cases of dengue hemorrhagic fever (DHF) in French Guiana. Forty cases met the World Health Organization definition of clinical DHF: 32 were grade II, seven were grade III, and one was grade IV and fatal. Eighteen cases were confirmed in the laboratory and 12 were probable; there was no proof of the dengue etiology for the remaining patients.
TL;DR: The Ribeirao Preto epidemic has thus, been set within the context of the spread of the disease at global level, in the Americas, and particularly in Brazil and S. Paulo State.
Abstract: A dengue fever epidemic which occurred in Ribeirao Preto County, S. Paulo State, Brazil, during the period November, 1990 to March, 1991 has been analysed else where. The general aspects of dengue epidemiology and control have been reviewed in this article. Emphasis is given to the analysis of some factors involved in the risk of dengue haemorrhagic fever and ecological aspects of the vector, as well as to the appropriateness of strategies for dengue eradication or control. Epidemiological characteristics of dengue, mainly those related to its occurrence in different geographical areas and periods of time are described. The Ribeirao Preto epidemic has thus, been set within the context of the spread of the disease at global level, in the Americas, and particularly in Brazil and S. Paulo State.
TL;DR: It was shown that both IL-1 and tumor necrosis factor-alpha are secreted from monocytes within 4 h after DV infection, but there was no increase inIL-1 secretion by virus-stimulated monocytes from dengue fever patients compared with healthy controls, and a new 600-kDa IL- 1 inhibitor from the supernatants of DV-infected monocytes was identified.
Abstract: Dengue hemorrhagic fever-dengue shock syndrome, the most severe manifestation of an acute dengue virus (DV) infection, is endemic in Southeast Asia. Antibody-dependent enhancement of DV growth in mononuclear phagocytes is thought to be the mechanism whereby preexisting dengue antibodies confer excess risk for this outcome. Interleukin-1 (IL-1) may play an important role in the pathogenetic mechanisms that cause dengue fever and shock. It was shown that both IL-1 and tumor necrosis factor-alpha are secreted from monocytes within 4 h after DV infection. However, there was no increase in IL-1 secretion by virus-stimulated monocytes from dengue fever patients compared with healthy controls. Significant amounts of IL-1 were secreted by DV-infected monocytes in the presence of aggregated immunoglobulin or immune complexes. In addition, a new 600-kDa IL-1 inhibitor from the supernatants of DV-infected monocytes was identified. This inhibitor may cause immunosuppression and influence the process of DV infection.
TL;DR: In Senegal, Dengue-2 virus appears to be maintained in an enzootic cycle and, therefore, plays an expanding role in human disease and increases the need for effective surveillance in mosquito populations.
Abstract: During 1990, Dengue-2 (DEN-2) virus was isolated for the first time from mosquitoes (Aedes furcifer, six isolates; Ae. taylori, six isolates; Ae. luteocephalus, seven isolates) collected during an epidemic in which DEN-2 virus also was isolated from humans. Numerous isolations have been made previously from mosquitoes in the absence of human infection. In Senegal, DEN-2 virus appears to be maintained in an enzootic cycle and, therefore, plays an expanding role in human disease and increases the need for effective surveillance in mosquito populations.
TL;DR: The data presented suggest a possible mechanism whereby infected monocytes undergoing diapedesis through blood vessel walls might differentiate sufficiently during the process to release virus and cytokines at localized sites on blood vessels.
Abstract: This study describes the susceptibility to dengue virus infection of a monocytic cell line at different states of differentiation. Infectious virus titres increased in undifferentiated U937 cells following infection with clinical isolates but only when the cells were infected via their Fc receptors. No c.p.e. was observed and virus was not secreted into supernatant fluid. Once differentiated, cells were susceptible to infection either with virus alone or with virus-antibody complexes. Infection was cytolytic and virus was released into the supernatant fluid. Similar results were obtained with freshly isolated peripheral blood monocytes. Increased blood vessel permeability, which occurs in dengue haemorrhagic fever and dengue shock syndrome patients, has been correlated with secondary heterotypic infections and has been postulated to arise from antibody-enhanced infection of monocytes. The data presented suggest a possible mechanism whereby infected monocytes undergoing diapedesis through blood vessel walls might differentiate sufficiently during the process to release virus and cytokines at localized sites on blood vessels.
TL;DR: An elevated IL-6 level was positively associated with severity of dengue infection in both children and adults, but IL-1 beta level was negatively associated with seriousness in adults.
Abstract: Recently, a strong correlation between high concentration of tumor necrosis factor (TNF alpha) in blood and severity of dengue hemorrhagic fever/dengue shock syndrome has been reported from Asia and the Pacific. We wished to determine if a similar relationship could be found in dengue patients in the Americas where adult patients with severe syndromes have been observed more frequently than in Asia where severe cases have been observed mostly among children. The concentrations of interleukin-1 (IL-1 beta) in hospitalized adult groups were significantly lower than that in outpatient adults. In contrast, the levels of interleukin 6 (IL-6) were significantly higher in hospitalized adults and children than in the corresponding outpatients. Levels of TNF alpha were higher in hospitalized children than in outpatient children or hospitalized adults. There was no significant difference in the levels of these three cytokines among hospitalized patients with or without hemorrhagic manifestations. Thus, an elevated IL-6 level was positively associated with severity of dengue infection in both children and adults, but IL-1 beta level was negatively associated with severity in adults.
01 Jan 1994
TL;DR: In this paper, reverse transcription and polymerase chain reaction (RT-PCR) was used to detect the dengue virus within 3 hours of infection using cultured mosquito cells.
Abstract: Serum specimens from patients with imported dengue fever and dengue hemorrhagic fever were directly subjected to reverse transcription and polymerase chain reaction (RT‐PCR) without any RNA purification. The amplified virus genome was detected within 3 hours. The results of PCR corresponded closely to the results of virus isolation using cultured mosquito cells, suggesting that direct RT‐PCR procedure greatly facilitates rapid diagnosis of dengue infection. © 1994 Wiley‐Liss, Inc.
TL;DR: There is no specific treatment for dengue; hydration is important as well as aggressive fluid management if hypotension develops, and it is important to avoid aspirin and salicylates.
TL;DR: Serum specimens from patients with imported d Dengue fever and dengue hemorrhagic fever were directly subjected to reverse transcription and polymerase chain reaction without any RNA purification, suggesting that direct RT‐PCR procedure greatly facilitates rapid diagnosis of denge infection.
Abstract: Serum specimens from patients with imported dengue fever and dengue hemorrhagic fever were directly subjected to reverse transcription and polymerase chain reaction (RT-PCR) without any RNA purification. The amplified virus genome was detected within 3 hours. The results of PCR corresponded closely to the results of virus isolation using cultured mosquito cells, suggesting that direct RT-PCR procedure greatly facilitates rapid diagnosis of dengue infection. © 1994 Wiley-Liss, Inc.
Journal Article•
TL;DR: Serological studies showed that both Ross River and dengue viruses have probably been introduced into New Zealand by viraemic travellers on many occasions and although some local mosquitoes can transmit these viruses in the laboratory, there is no evidence of local spread of virus from these imported cases.
Abstract: Aim To determine the prevalence of antibodies to Ross River and dengue viruses in sera from New Zealand residents and travellers and to assess the potential of local mosquitoes to act as vectors of these viruses. Method Serum specimens from several population groups were examined by haemagglutination-inhibition and neutralisation tests for antibodies to Ross River and dengue viruses between 1975 and 1993. During this period dengue was active in South East Asia, Australia and the Pacific, and a major epidemic of Ross River infection occurred in the Pacific. Two New Zealand mosquito species were tested for their ability to transmit by bite after they had been fed or injected with these viruses. Results Ten percent of 1869 sera from patients suspected of contracting dengue, and 43% of 183 patients suspected of contracting Ross River virus, while overseas, were antibody positive. Many patients showed antibody rises which indicated that they were probably viraemic on entry to this country. Dengue viruses were isolated in Dunedin from two patients with dengue haemorrhagic fever contracted overseas. Antibody studies of persons who had not travelled outside New Zealand provided no evidence of local transmission of these viruses. Two local mosquitoes, Aedes notoscriptus from the Auckland area, and Aedes australis from the Otago area, were able to transmit one or both these viruses under laboratory conditions. Conclusions The serological studies showed that both Ross River and dengue viruses have probably been introduced into New Zealand by viraemic travellers on many occasions. Although some local mosquitoes can transmit these viruses in the laboratory, there is no evidence of local spread of virus from these imported cases. Changing environmental conditions such as global warming with concomitant effects on vector distribution, increasingly rapid air travel by viraemic persons and the accidental introduction of new vector mosquitoes, particularly Aedes albopictus, could pose a threat in view of the high percentage of New Zealand residents with no protective antibody.
TL;DR: Results indicate that E-specific clones are serotype specific and HLA-DR7 restricted in these two donors and suggest that a common epitope on E protein may be recognized.
Abstract: We analyzed dengue virus-specific CD4+ CD8- cytotoxic T lymphocytes (CTL) at the clonal level to further understand their role in dengue virus infections. Stimulation of peripheral blood mononuclear cells from two dengue virus type 4 (D4V)-immune donors with live D4V or noninfectious D4V antigen generated 17 HLA class II-restricted CD4+ CTL capable of specific lysis of dengue virus antigen-treated autologous lymphoblastoid cell lines. Thirteen clones were D4V specific, three clones were cross-reactive for D2V and D4V, and one clone was cross-reactive for D1V, D3V, and D4V. Antigen recognition by six D4V-specific clones and three D2V- and D4V-cross-reactive clones was restricted by HLA-DR7. Five D4V-specific CD4+ CTL clones lysed autologous lymphoblastoid cell lines infected with a dengue virus-vaccinia virus recombinant containing the E gene of D4V, whereas three serotype-cross-reactive CTL clones did not. These results indicate that E-specific clones are serotype specific and HLA-DR7 restricted in these two donors and suggest that a common epitope on E protein may be recognized. E protein-specific CD4+ CTL may be important mediators of virus clearance especially during reinfection with the same serotype as that in primary infection by providing help for virus-specific antibody production and lysis of virus-infected cells.
TL;DR: A prospective investigation of febrile illnesses among US forces in Somalia revealed dengue viruses as an important identifiable cause and the detection of d Dengue 3 in north-east Africa is recorded.
TL;DR: The capacity for oral infection, dissemination, and transmission of the dengue-2 candidate vaccine virus DEN-2 PDK53 and an isolate from a vaccinate individual, den-2 Ia8, were compared with the parent strain of the vaccine virus.
Abstract: The capacity for oral infection, dissemination, and transmission of the dengue-2 candidate vaccine virus DEN-2 PDK53 and an isolate from a vaccinate individual, DEN-2 Ia8, were compared with the parent strain DEN-2 16681 Capacity for oral infection and dissemination to the brain and salivary gland tissues were significantly lower in the first two than in the parent strain (P < 0001) Replication was more than 100 times higher for the parent strain when compared with the dengue-2 candidate vaccine virus Transmission was not demonstrated in the mosquitoes orally infected with DEN-2 PDK53 and DEN-2 Ia8, whereas transmission was achieved in 57% (8 of 14) of mosquitoes infected with the parent virus strain Using immunofluorescence, viral antigen was detected in the mosquitoes infected with DEN-2 PDK53 and DEN-2 Ia8 It was seen mainly in the form of specks scattered in some parts of the tissues, and was strikingly different from that seen in the parent strain, in which major parts of the tissues contained viral antigen in the form of rings and specks The biological markers of DEN-2 PDK53 and DEN-2 Ia8 retained the biological characteristic of the vaccine after a mosquito passage and a human and mosquito passage, respectively
Journal Article•
TL;DR: In 1987, 505 serologically confirmed dengue infection patients were admitted to the Department of Pediatrics, Chulalongkorn Hospital, Bangkok, Thailand and 14 patients had unusual manifestations which were mostly encephalopathic and hepatopathic.
Abstract: In 1987, 505 serologically confirmed dengue infection patients were admitted to the Department of Pediatrics, Chulalongkorn Hospital, Bangkok, Thailand. Fourteen patients had unusual manifestations which were mostly encephalopathic and hepatopathic. Patients who had unusual manifestations tended to be in the younger age group and had higher mortality.
TL;DR: It is concluded that neither dengue-3 virus is neurovirulent for cynomolgus monkeys and no differences were observed between the DEN-3 parent and vaccine viruses.
Abstract: Investigation of monkey neurovirulence of dengue-3 viruses (DEN-3, 16562) was undertaken to provide an evaluation of the relative safety of virus strain attenuated for potential use of live virus vaccine. Ten flavivirus-negative, cynomolgus monkeys (Macacafascicularis) were used in the test. The animals were inoculated intrathalamically, intraspinally and intramuscularly with DEN-3 PGMK 33 attenuated live virus vaccine (6 monkeys): parent virus (2) and control cell culture fluid (2). Blood samples were collected on days 0, 1, 2, 4, 6, 8, 10, 12 and 21 for virus isolation and days 0 and 21 or 22 for serologic testing. One monkey with DEN-3 (16562) PGMK 33 candidate vaccine had detectable viremia on day 10. By day 21, all recipients of PGMK 33 and both monkeys with DEN-3 parent virus developed serum neutralizing antibodies to DEN-3 titers ranged from 56-320. The monkeys showed no evidence of illness and none died of dengue infection. Histopathological examination of tissue collected on day 21 or 22 revealed only minimal neurovirulence lesions as scored by the routine grading system. No differences were observed between the DEN-3 parent and vaccine viruses and it is concluded that neither virus is neurovirulent for cynomolgus monkeys.