WHO fights dengue haemorrhagic fever.
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Asia, Southeastern↗
Biomedical subjects
S B Halstead
Publications and source records attributed to S B Halstead.
Viral hemorrhagic fevers.
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Antigen-Antibody Complex↗
The Alexander D. Langmuir Lecture. The pathogenesis of dengue. Molecular epidemiology in infectious disease.
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Age Factors↗
In vitro virulence marker: growth of dengue-2 virus in human leukocyte suspension cultures.
We wished to find a simple, biologically relevant method to evaluate the virulence of dengue viruses for human beings. Since cells of mononuclear phagocyte lineage may be important sites of dengue infection in primates, we evaluated the permissiveness of these cells to dengue virus as a correlate of virus virulence. Two wild-type, large-plaque, monkey-virulent dengue-2 virus strains and two small-plaque, monkey-avirulent dengue-2 virus strains were evaluated for their ability to replicate in human peripheral blood leukocyte cultures supplemented with enhancing antibody. One of the small-plaque strains was demonstrated to have reduced virulence for man. Wild-type dengue-2 viruses replicated readily in peripheral blood leukocyte suspension cultures, whereas small-plaque dengue-2 strains did not. Differences between our data and results obtained by other workers employing adherent peripheral blood leukocytes are discussed. Antibody-enhanced growth of dengue virus in suspension cultures of human peripheral blood leukocytes gives promise of being a simple in vitro system for characterizing dengue virus virulence.
Cells, Cultured↗
Suppression of dengue virus replication in vitro by rimantadine hydrochloride.
The effects of rimantadine on dengue virus replication were examined in a variety of tissue culture systems. The growth of dengue virus type 2 in human peripheral blood leukocytes (PBL) was completely suppressed when rimantadine was included in the culture medium at a concentration of 25 microgram/ml. Similarly, rimantadine caused a significant inhibition of dengue virus replicaton in cultures of rhesus monkey PBL. Addition of drug into virus-infected LLC-MK2 cell cultures caused a decrease in the production of all four types of dengue virus. Maximal inhibition of dengue virus replication by rimantadine was observed when the drug was added immediately following the viral adsorption period. Rimantadine did not induce may cytopathic effects on either LLC-MK2 cells or PBL at concentrations less than 75 microgram/ml. These findings demonstrate that rimantadine is an effective inhibitor of dengue virus replication in vitro, and indicate a need for further examination of the efficacy of rimantadine against severe dengue virus disease.
Adamantane↗
Propagation of dengue viruses in murine cell cultures.
Dengue viruses were cultivated in Balb 3T12-3 cells, a continuous line of cells derived from mouse embryo cell cultures. Optimal serum concentrations were determined for maximal kinetics of virus replication. All four types of dengue viruses replicate in these cells, and peak virus titers were obtained by 72 hours post-infection. The successful growth of dengue viruses in a continuous line of mouse cells should allow for more extensive studies examining the cellular immune response to dengue virus infection in murine models.
Animals↗
An explanation for enhanced virus plaque formation in chick embryo cells.
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Animals↗
Studies on dengue 2 virus infection in cyclophosphamide-treated rhesus monkeys.
Dengue 2 virus (D2V) replication has been demonstrated in cultured primate mononuclear phagocytes, mitogen treated lymphocytes and lymphoblastoid cells. To determine which of these cell types might play an important role in sustaining infection in vivo, nine rhesus monkeys were immunosuppressed with cyclophosphamide and then infected with D2V. Maintenance dose which held total white blood cell counts to less than 3000/mm3 ablated both primary and secondary antibody responses. Six successfully immunosuppressed animals circulated virus and infected monocytes in blood for prolonged periods. Virus was recovered from lymphatic organs and visualized in tissue mononuclear leukocytes in two subjects dying during the experimental period. The results argue against the hypothesis that lymphoblasts play an important role in dengue virus infection but are consistent with the possibility that mononuclear phagocytes are the site of viral replication in vivo.
Animals↗
Inhibition of dengue virus replication by amantadine hydrochloride.
The effect of amantadine hydrochloride (1-adamantanamine hydrochloride) on dengue virus replication was examined in vitro. Amantadine decreased the titers of all four types of dengue viruses grown in LLC-MK2 cells by greater than 90% at concentrations of 50 micrograms/ml. There was no evidence for any cytopathic effect of the drug at concentrations less than 100 micrograms/ml. Studies of the time of addition showed that the antiviral effect was maximal when drug was added to virus cultures immediately after the viral adsorption period. In addition, amantadine caused a marked reduction in the growth of dengue virus type 2 in both human and rhesus peripheral blood leukocytes without affecting cell viabili ty. These findings demonstrate that amantadine significantly inhibits the replication of dengue viruses in vitro and indicate a need to determine the efficacy of this drug against dengue virus infections in vivo.
Amantadine↗
Transmission of dengue 1 and 2 viruses in Greece in 1928.
In August-September 1928 appoximately 650,000 residents of Athens and Piraeus contracted dengue fever, and 1,061 died. We were interested in the etiology of this severe epidemic in which many cases resembled dengue hemorrhagic fever or the dengue shock syndrome, and have attempted a retrospective seroepidemiological study. Serum specimens were obtained from 111 residents of Athens or Piraeus who were born in 1927 or 1928, and were studied by plaque reduction neutralization test for antibodies to dengue 1-4 viruses. Of 75 persons born in 1928, 20 (27%) had monospecific dengue 1, 10 (13%) had monospecific dengue 2, and 1 (1%) had dengue 1 and 2 neutralizing antibodies. When prevalence of neutralizing antibody was analyzed by month of birth in 42 individuals, evidence of both dengue 1 and 2 infections was found in persons born in January-July, but only dengue 2 antibody was detected in those who were born after July. This study dates dengue 1 and dengue 2 transmission to 1928, allowing for the possibility that sequential infections with these viruses could have played a pathogenetic role in the outbreak.
Antibodies, Viral↗
Enhancement of dengue virus infection in monocytes by flavivirus antisera.
Enhanced dengue 2 virus (D2V) infection in suspension cultures of human peripheral blood mononuclear phagocytes (PBL) produced by subneutralizing concentrations of dengue antisera has been described previously. In this study, the enhancement phenomenon was found to be a general property of representative flavivirus antisera. All except one of 24 antisera, which had been raised by 1-3 injections of flaviviruses in rabbits, enhanced the growth of dengue 2 virus in human PBL. Flavivirus antisera showing the greatest level of cross-reactivity against a battery of 42 flavivirus antigens in the hemagglutination-inhibition test were most potent in enhancing dengue replication in PBL cultures. Cross-neutralizing reactivity did not relate to enhanced D2V infection. However nearly one-half of studied flavivirus antisera neutralized D2V at dilutions of 1:10 or 1:20. Heterotypic D2V neutralizing antibody could serve as a "brake" on infection enhancement in vivo. Observations should be made in the field to look for possible enhancement of dengue infection in heterotypic flavivirus immunes.
Adult↗
Dengue haemorrhagic fever--a public health problem and a field for research.
Dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS) is an enigmatic and growing public health problem which is confined at present to countries of South-East Asia. Since 1956, over 350 000 patients have been hospitalized and nearly 12 000 deaths have been reported. Dengue viruses, a group of four flaviviruses, are transmitted to man by Aedes aegypti. Currently, dengue viruses are actively transmitted in 61 countries which circle the globe in the tropical zone and have a combined population of 1500 million. Because the precise antecedents to DHF/DSS are unknown, the public health hazard posed by this syndrome is potentially worldwide. Epidemiological studies in South-East Asia clearly link DHF/DSS to individuals who have had a previous dengue infection or who have acquired maternal dengue antibody. Such antibody may serve as an opsonin, enhancing dengue virus infection of mononuclear phagocytes-the type of cell in man to which dengue infection may be confined. Antibody-mediated infection of these cells is the central concept in the hypothesis of immune infection enhancement. This hypothesis provides a conceptual framework for design of future research. There is an urgent need for a comprehensive identification of "risk factors" in DHF/DSS. This research could be approached by undertaking comparative prospective epidemiological studies in dengue-endemic areas with and without DHF/DSS. Although important progress is being made in the development of attenuated dengue vaccines for each dengue type, a clearer understanding of the pathogenesis of DHF/DSS may be required to provide guidelines for safe and lasting immunoprophylaxis in man.
Africa, Western↗
Incidence of infectious mononucleosis at the Universities of California and Hawaii.
The observed rates of heterophil-positive infectious mononucleosis at the University of California at Davis and the University of Hawaii at Manoa were 1,212 and 37 per 100,000 students per academic year, respectively. The data collected suggest that the extraordinarily low incidence at the University of Hawaii may be due to the following factors: (1) underutilization of the student health service by students with infectious mononucleosis; (2) low proportion of Epstein-Barr virus-seronegative students; (3) high proportion of Asian students who appear to be less likely to develop heterophil-positive infectious mononucleosis; and (4) possible low efficiency in the transmission of primary Epstein-Barr virus infections.
Adolescent↗
In vivo enhancement of dengue virus infection in rhesus monkeys by passively transferred antibody.
Five pairs of juvenile, dengue virus-susceptible rhesus monkeys were given normal or dengue-immune human cord-blood serum injected intravenously to a final dilution of 1:300. The pool of immune human cord-blood serum had a titer of antibody to dengue type 2 virus (D2V) of 1:140 in the plaque-reduction neutralization test and a titer of human monocyte infection enhancement of greater than 1:2,000,000. Fifteen minutes after inoculation of serum, animals were infected with D2V (strain no. 16681). Daily titers of viremia were always higher in the animals that had received antiserum to D2V than in animals that had received normal cord-blood serum. Ratios of infection enhancement ranged from 2.7 to 51.4. The demonstration of antibody dependence of dengue virus infection in subhuman primates--a complex, outbred experimental host--supports the hypothesis that the severity of dengue in humans is regulated by antibody.
Animals↗
Effect of immune status on dengue 2 virus replication in cultured leukocytes from infants and children.
Cord blood leukocytes from neonates with maternal dengue antibody supported dengue 2 virus replication in vitro; those from neonates without maternal antibody did not. Cord bloods of infants born to dengue-immune mothers contained a potent enhancing factor which gradually decayed with age and which was absent from neonates born to nonimmune mothers. Permissiveness of cultures of washed peripheral blood leukocytes from infants with maternal antibody declined steadily with increasing age in parallel with the decay of maternal antibody, and the leukocytes were no longer permissive after 10 to 12 months. The demonstration of a dengue maternal infection-enhancing factor in human cord blood from dengue-immune mothers supports the hypothesis that severe primary dengue hemorrhagic fever with shock seen in Bangkok infants is related to maternal immune status.
Age Factors↗
Absence of leukocytes permissive to dengue 2 virus in the acute phase of dengue hemorrhagic fever.
Patients with primary dengue infection developed dengue 2 virus (D2V) permissive peripheral blood leukocytes (PBL) 2--3 weeks after infection. PBL from healthy individuals with dengue antibody were permissive to D2V in vitro, suggesting that immunologically mediated in vitro D2V permissiveness persists for a relatively long time after recovery from dengue infection. However, PBL obtained from second infection dengue hemorrhagic fever patients did not support D2V growth during the acute phase of illness but did so during convalescence. Leukocytes from dengue-immune patients with typhoid fever or non-dengue viral illness were permissive throughout both acute and convalescent phases of illness although there was tendency for increased permissiveness during convalescence. Acute phase PBL from DHF patients synthesized and secreted dengue neutralizing antibody in culture. Absence of D2V replication in these cultures was strongly, but not completely, correlated with antibody production. Other immunological mechanisms, in addition to antibody, may be operating in vitro or in vivo during acute phase dengue hemorrhagic fever to alter the permissiveness of PBL to D2V infection.
Adolescent↗
Oral polio vaccine. Effect of booster vaccination one to 14 years after primary series.
We studied the persistence of antibody after vaccination and the response to booster revaccination with trivalent oral polio vaccine (TOPV) administered at varied intervals after the primary series in a large group of children. Decline in antibody was related to intervals since last vaccination, and not to sex, age, age at primary vaccination, or type and number of previous administrations. Geometric mean titers of neutralizing antibody were 11.3 for type 1 and 8.0 for types 2 and 3 poliovirus when vaccine had been given within the previous year, declining to 3.2, 3.0, and 2.1 for types 1, 2, and 3 after nine years. Most children with an initial titer of 4 or less responded to revaccination with a fourfold or greater increase in titer of IgG. Geometric mean titers for all three types of polio dropped to this level when last TOPV administration had been five to six years or more.
Adolescent↗
Specific lethality of silica for human peripheral blood mononuclear phagocytes, in vitro.
Human peripheral blood mononuclear cells, cultured in the presence of 100 microgram/ml protein-coated silica particles, were studied to determine changes in number and function of monocytes, immunoglobulin bearing (B), sheep red blood cell rosetting (T) lymphocytes and the effector cells of antibody dependent cell-mediated cytotoxicity (ADCC). After 24-48 h, phagocytic cells were effectively eliminated from culture but there was no significant reduction in number or function of T or B lymphocytes or in ADCC to cell line targets. ADCC to erythrocyte targets was inhibited but not completely blocked. It is concluded that silica is a specific toxin for human peripheral blood mononuclear phagocytes and may be useful in in vitro immunological studies as a means of eliminating or determining the role of these cells without resort to separation methods which result in losses of cells other than monocytes.
Animals↗