Showing papers on "Dengue fever published in 1973"

The potential pathogenic role of complement in dengue hemorrhagic shock syndrome.

Abstract: In Bangkok, Thailand, 49 of 127 patients with dengue hemorrhagic fever experienced shock. The concentration of nine complement proteins measured in serial serum samples decreased during shock with the exception of C9. C3 and C5 were reduced to 20 to 40 per cent of normal in severe cases. Decrease of plasma fibrinogen, appearance of fibrinogen split products and thrombocytopenia indicated occurence of intravascular coagulation. Metabolic studies of C3 and C1q, performed on 24 patients, indicated a markedly enhanced fractional catabolic rate especially during shock. These results support the concept that activation of complement can constitute a major factor in the pathogenesis of dengue hemorrhagic shock. (N Engl J Med 289:996–1000, 1973)

Studies on the Pathogenesis of Dengue Infection in Monkeys. II. Clinical Laboratory Responses to Heterologous Infection

Abstract: Laboratory responses to a second inoculation of a dengue virus were studied in 118 rhesus monkeys challenged at intervals of two, six, 12, and 26 weeks. Nine animals received the same virus twice; the others received a heterologous type. A single animal manifested leukocytosis, thrombocytopenia, elevation of prothrombin time, and decrease in complement during an infection due to dengue 2 virus that followed a pimary dengue 4 infection at an interval of three months. A mild thrombocytopenia was significantly correlated with secondary dengue 2 infections. A sharp decrease in total complement was observed early after secondary infection with dengue 2 in six of eight monkeys. In secondary dengue 1 and 4 infections, titers of viremia were depressed, while viremia was not detected after secondary challenge with dengue 3. Peak titers of secondary dengue 2 viremia were 13-fold higher than peak titers in primary dengue 2 infections. The greater production of virus in certain secondary infections due to dengue viruses could be a controlling mechanism in the postulated immunologic injury in dengue shock syndrome in man.

Studies on the Pathogenesis of Dengue Infection in Monkeys. I. Clinical Laboratory Responses to Primary Infection

Abstract: Virologic, serologic, and clinical responses to infection were studied in 122 Macaca mulatta monkeys and 17 monkeys of three other species that were inoculated with dengue 1-4 viruses passaged in tissue culture. Susceptible rhesus monkeys, inoculated with either high (1037-10".pfu) or low (8-50 pfu) doses of virus always developed antibody. Frequently with dengue 2 infection, but less frequently with dengue 1 infection, lymphadenomegaly, depression of leukocyte count, and lymphocytosis were noted. In approximately 90% of infected animals viremia began two to six days after inoculation; 90% of dengue 2 and 4 viremias lasted six days or less; the average duration of dengue 1 viremia was somewhat longer, and of dengue 3 viremia shorter than this. HAI titers to the homologous antigen in convalescent sera were usually twofold higher than titers to heterologous dengue viruses; antibody response to dengue 4 infection was relatively specific. No abnormalities were observed in serial hematocrit, prothrombin time, and determinations of total protein. Levels of complement in serum rose several days after the start of serial bleedings in both infected and control animals. The courses of infection due to dengue viruses are similar in humans and monkeys.

Studies on the Pathogenesis of Dengue Infection in Monkeys. III. Sequential Distribution of Virus in Primary and Heterologous Infections

Abstract: Sequential localization in tissue of dengue viruses was studied in 31 primary and eight secondary infections in rhesus monkeys. In ten animals sacrificed before viremia in primary infection, virus was rapidly disseminated from the inoculation site to regional lymph nodes and then to lymphatic tissue throughout the body. Early in the viremic period virus was recovered only from lymph nodes, while two to three days later there was evidence of dissemination to skin and other tissues. Virus was recovered from skin, lymph nodes, and several leukocyte-rich tissues for three days after the termination of viremia. Sequential tissue studies showed virus in circulating leukocytes, in multiple skin sites, and in the upper respiratory tract at the end or just after the termination of viremia. In preliminary experiments, the rate of recovery of virus from tissues was higher in secondary infection than in primary infection. This study suggests that the amount of intracellular infection increases toward the end of the viremic period, abruptly ending one to two days later. This phenomenon correlates closely with the time of onset of shock in human dengue infection.

Replication of Dengue Virus Type 2 in Aedes albopictus Cell Culture

Abstract: The replication of type 2 dengue (D-2) virus in Aedes albopictus (Aal) mosquito cell cultures differed from that in vertebrate (LLC-MK2) rhesus monkey kidney cells. Virus readily replicated in Aal cells at either 30 or 37 C, but had no apparent effect on the host cell. Persistent infection was established with continual virus production for at least 6 months, although the virulence of progeny virus for both suckling mice and LLC-MK2 cells became attenuated. Density gradient analysis of infected Aal cell supernatant products indicated that only complete virus was released, in contrast to infected LLC-MK2 cells which also released incomplete virus. The surface antigens of the virus produced in Aal cells appeared to be considerably modified in that antiserum to vertebrate cell-produced D-2 virus did not block hemagglutination, whereas anti-Aal cell antiserum did. Virus infectivity could be neutralized by the antiserum to D-2 virus grown in vertebrate cells, however. Virus produced in LLC-MK2 cells did not demonstrate a similar host-cell modification. These results may reflect a difference in the mechanism by which D-2 virus matures in Aal cells.

Arbovirus (dengue type) as a cause of acute myocarditis and pericarditis.

Abstract: The arbovirus (arthropod-borne) comprises a large group, now numbering more than 200 types, of which at least 50 have been associated with disease in man. The best known ones are found in Group A and Group B. They commonly manifest with fever, headache, general and local pain, and less commonly rash and lymphadenopathy. Many virus illnesses have been associated with myocarditis and pericarditis and it is only recently that a large number of potential causes of myocarditis have been appreciated. We wish to report a case of myocarditis with pericarditis caused by dengue virus. Two others are briefly mentioned for one has already been the subject of another communication (Nagaratnam and de Silva, I972).

An epidemic of dengue on Tahiti associated with hemorrhagic manifestations.

Abstract: During the course of an outbreak of dengue type 2 on the island of Tahiti, French Polynesia, severe hemorrhagic disease was observed in an unusual number of patients shortly after the onset of a febrile illness. In at least 33 instances, these hemorrhages were severe enough to require hospitalization and 3 patients died. Gastrointestinal bleeding was the most common type of severe hemorrhage observed and gross hematuria was next most common. The available data suggested that most of the hemorrhagic episodes were etiologically related to dengue virus.

Human Antibody to Dengue Soluble Complement-Fixing (SCF) Antigens

Abstract: Soluble complement-fixing (SCF) antigens were prepared to dengue viruses, types 1 to 4, from infected suckling mouse brain. While these non-structural proteins previously had been shown to have group- and type-specific antigenic determinants and to circulate in infected mice, their participation in human dengue infection was never established. Human acute and convalescent sera from primary and secondary dengue infections were tested for antibody to SCF antigens. At two antigen units, one of nine primary convalescent samples had antibody to a single type of dengue SCF, none of 11 secondary acute-phase sera had SCF antibody while all of 22 convalescent-phase samples had relatively high titers to two or more SCF antigens. With higher antigen concentrations, none of eight primary convalescent samples and only one of nine secondary acute-phase sera had antibody to dengue 2 SCF antigen. Sucrose gradient ultracentrifugation showed the antibody activity in the secondary convalescent-phase sera to be of the IgG class, suggesting prior antigenic exposure in these hosts. The inability to detect anti-SCF in the primary convalescent and secondary acute samples was not due to IgM interference as demonstrated with ethanethiol reduction experiments. This study has demonstrated that SCF antibody is produced in humans allowing for the possibility, as postulated, that these antigens participate in dengue immunopathogenesis. The inability to detect antibody during the acute phase of secondary dengue infections and in the convalescent sera from primarily infected humans requires further study.

Arbovirus studies in Luanda, Angola. 2. Virological and serological studies during an outbreak of dengue-like disease caused by the Chikungunya virus.

Abstract: An outbreak of dengue-like disease was observed in Luanda, Angola, at the end of 1970 and beginning of 1971. Chikungunya virus was isolated from the blood of a patient with typical symptoms of dengue and from a pool of Aedes aegypti mosquitos. A survey for antibodies to arboviruses in the sera of persons living in Luanda showed that the Chikungunya virus was indeed responsible for the outbreak. The fact that this outbreak immediately preceded and continued concurrently with a yellow fever epidemic in Luanda shows that two arboviruses from different antigenic groups may circulate simultaneously in the same ecological area.

Sequential immunization procedure against Group B arboviruses using living attenuated 17D yellow fever virus, living attenuated Langat E5 virus, and living attenuated dengue 2 virus (New Guinea C isolate).

Abstract: Spider monkeys immunized sequentially with living 17D yellow fever virus, living attenuated Langat E5 virus, and living attenuated dengue 2 virus (New Guinea C isolate) responded with high hemagglutinating-inhibition antibody titers against 21 Group B arbovirus antigens that were tested. Such monkeys also responded with neutralizing antibodies against 20 Group B arboviruses that were tested. These vaccinated monkeys were protected against subcutaneous challenges with dengue serotypes 1, 2, 3 or 4, Russian spring-summer encephalitis virus, Kyasanur Forest Disease virus, Omsk hemorrhagic fever virus, Japanese encephalitis virus, Murray Valley encephalitis virus, West Nile virus, and Kadam virus. The protection against these viruses was based on a much lower viremia, or absence of histologic lesions in the central nervous system, or absence of an antibody booster response. The 3-virus sequential immunized spider monkeys were also protected against Modoc virus as determined by viremia studies, in spite of the fact that no detectable serum neutralizing antibodies were found in these animals at the time of challenge. The development of the sequential immunization procedure is discussed.

Surveys of Haemagglutination-Inhibiting Antibody to Arboviruses in Aborigines and Other Population Groups in Northern and Eastern Australia, 1966–1971

Abstract: Surveys of Aboriginal settlements by haemagglutination-inhibition tests against arboviruses of Groups A and B showed very low prevalence of antibody in eastern Queensland, very high prevalence in north-west Queensland and some settlements in the Northern Territory, and intermediate prevalence at other settlements in the Northern Territory. Sera from about 1500 patients received from the general community of east coastal Queensland for diagnostic serological tests, but with no evidence of current arbovirus infection, showed some differences in age distribution of antibody between Ross River virus of Group A (with prevalence rising to a plateau level of 50% from age 30) and Group B (with few reactions in younger age groups and steady rise in prevalence from age 20 to almost 90% beyond age 60). Sets of sera reactive to one Group B arbovirus were titrated by haemagglutination-inhibition test to 8 members of the Group; mean titres to each virus were computed and compared. 2 distinct patterns of response were defined, reacting significantly to both dengue and Murray Valley encephalitis subgroups (east coastal Queensland), or only to the Murray Valley encephalitis subgroup (north-west Queensland and Northern Territory). These findings, the history of extensive epidemics of dengue in eastern Queensland, and other laboratory studies described in this and previous papers, suggest that the broadly-reactive antibody is due to dengue infection. The long persistence of high-titre, broadly reactive antibody after dengue infection in Queensland and elsewhere is seen as an interesting phenomenon worthy of further study. Most of the many reactions to Group A viruses detected in the study were clearly to Ross River virus, but 15 patients gave serological results suggesting past infection with Sindbis virus. One of the 15 had rising titres following a mild febrile illness with lymphadenopathy and rash, suggesting that Sindbis virus may have caused the illness.

The 1970 yellow fever epidemic in Okwoga District, Benue Plateau State, Nigeria. 3. Serological responses in persons with and without pre-existing heterologous group B immunity.

Abstract: Serological studies of persons infected with yellow fever (YF) during the 1970 epidemic in Okwoga District, Nigeria, indicated that epidemic YF occurred despite a high prevalence of pre-existing group B arbovirus immunity, which increased with age. The viruses involved were primarily dengue, Zika, and Wesselsbron. Patterns of responses of haemagglutination-inhibiting, complement-fixing, and neutralizing antibodies in primary YF and in superinfections are defined in this paper.