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Showing papers on "Dengue fever published in 1979"


Journal ArticleDOI
TL;DR: The demonstration of antibody dependence of dengue virus infection in subhuman primates--a complex, outbred experimental host--supports the hypothesis that the severity of d Dengue in humans is regulated by antibody.
Abstract: 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.

424 citations


Journal ArticleDOI
TL;DR: A study of Zika virus infections was carried out in four communities in Oyo State, Nigeria, and revealed a high prevalence of antibodies to Zika and three other flaviviruses used.
Abstract: A study of Zika virus infections was carried out in four communities in Oyo State, Nigeria. Virus isolation studies between 1971 and 1975 yielded two virus isolations from human cases of mild febrile illness. Haemagglutination-inhibition tests revealed a high prevalence of antibodies to Zika and three other flaviviruses used. The percentages of positive sera were as follows: Zika (31%), Yellow fever (50%), West Nile (46%), and Wesselsbron (59%). Neutralization tests showed that 40% of Nigerians had Zika virus neutralizing antibody. Fifty per cent of zika virus immune persons had neutralizing antibody to Zika alone or to Zika and one other flavivirus. A total of 121 sera had antibody to Zika virus; of these 48 (40%) also showed antibody to two other flaviviruses, and 12 (10%) had antibodies to three or more other viruses. The percentage of neutralizing antibodies to other flaviviruses in Zika virus immune sera was 81% to Dengue type 1, 58% to Yellow fever, 7% to Wesselsbron, 6% to West Nile and 3% to Uganda S.

306 citations


Journal ArticleDOI
TL;DR: The comparative susceptibility of 13 geographic strains of Aedes aegypti to oral infection with dengue viruses was studied by feeding the mosquitoes on a virus-erythrocyte-sugar suspension, suggesting that the factors controlling susceptibility were the same for all types.
Abstract: The comparative susceptibility of 13 geographic strains of Aedes aegypti to oral infection with dengue viruses was studied by feeding the mosquitoes on a virus-erythrocyte-sugar suspension. Significant variation in susceptibility to four dengue serotypes was observed among the geographic strains tested. Mosquito strains which were more susceptible to one serotype were also more susceptible to the other serotypes, suggesting that the factors controlling susceptibility were the same for all types. The amount of virus required to infect mosquitoes orally varied inversely with the susceptibility of the geographic strain. Thresholds of infection were not the same for dengue types 1, 2, 3 and 4. There was no apparent difference in infectivity between prototype and recently isolated strains of dengue types 1 and 3. Crossing experimentibility as the resistant parent. No difference was observed between resistant and susceptible mosquito strains in the rate or the amount of viral replication after infection by the parenteral route, or in their ability to transmit dengue 2 virus after infection by the oral route.

230 citations


Journal ArticleDOI
TL;DR: By incubating the mosquito cells at 32 degrees C, dengue viruses can be identified and typed within 6 days after inoculation, and the sensitivity of this method was compared with mosquito inoculation in comparative titrations of 16 low passage d Dengue virus strains.
Abstract: An improved method for the isolation and identification of dengue viruses is described. Viruses were isolated in mosquito cell cultures (C6/36 or AP-61), identified by indirect fluorescent antibody technique, and typed by complement-fixation test, using the cell culture fluid as antigen. The sensitivity of this method was compared with mosquito inoculation in comparative titrations of 16 low passage dengue virus strains. Although lower virus titers were obtained by the mosquito cell culture technique, its decreased sensitivity was compensated for by the much larger volume (588×) which could be assayed. By incubating the mosquito cells at 32°C, dengue viruses can be identified and typed within 6 days after inoculation.

196 citations


Journal ArticleDOI
TL;DR: Virological studies were carried out during an epidemic of dengue hemorrhagic fever in Central Java, Indonesia in 1976 and showed that many patients were circulating over 10(8) MID50 per milliliter d Dengue 3 virus for the first 3 days of illness and that viremia persisted for 5-6 days in some persons.
Abstract: Virological studies were carried out during an epidemic of dengue hemorrhagic fever in Central Java, Indonesia in 1976. Dengue virus was isolated from the acute sera of 45 of 69 patients (65%). The isolation rate was higher in primary than secondary cases. Dengue 3 was the predominant serotype being transmitted (27 isolates), but both dengue 1 (8 isolates) and dengue 4 (10 isolates) were also being transmitted. A composite picture of magnitude and duration of viremia showed that many patients were circulating over 108 MID50 per milliliter dengue 3 virus for the first 3 days of illness and that viremia persisted for 5–6 days in some persons. If all shock cases were considered, there was no relationship between dengue serotype and severity of disease. All three confirmed fatal cases, however, were associated with dengue type 3 infections.

121 citations


Journal Article
TL;DR: The findings suggest that the cutaneous rashes occurring in DHF are caused by an immunopathologic process.
Abstract: Fifty-three skin biopsy specimens obtained from the cutaneous rashes of patients who had dengue hemorrhagic fever (DHF) were studied by immunofluorescence technique. Six specimens showed deposits of IgM, beta 1 C-globulin, dengue antigen, and fibrinogen during the first week of fever. Some but not all of these components (IgM, beta 1 C, dengue antigen) were demonstrated in 29 specimens. Twenty-three of them yielded negative results. Granular deposits of IgM and beta 1 C appeared in the blood vessel walls of dermal papillae. Dengue antigen was seen in mononuclear cells that were closely infiltrated around the blood vessel wall in dermal papillae. Fibrinogen was located within or about the blood vessels. The findings suggest that the cutaneous rashes occurring in DHF are caused by an immunopathologic process.

78 citations


Journal ArticleDOI
TL;DR: Comparative studies showed that Ae.
Abstract: Entomological studies were carried out during a dengue hemorrhagic fever epidemic in Central Java in December 1976. Both Aedes aegypti and Aedes albopictus were widely distributed in Bantul, but the latter species was more abundant. Comparative studies on the vector competence of the two species showed that Ae. albopictus had a higher susceptibility than Ae. aegypti to oral infection with all four dengue serotypes. The two species were equally compentent in transmitting the Bantul strain of dengue 3 virus after parenteral infection. The data suggest that Ae. albopictus could have been an important vector in this epidemic, but no direct observations were obtained to define the respective contribution of either Ae. albopictus or Ae. aegypti.

59 citations


Journal Article
TL;DR: Circulating immune complexes were detectable in 80% of serum from patients with dengue haemorrhagic fever and correlated well with the clinical grading (severity of the disease), i.e. the maximum amount was shown in grade III.
Abstract: Circulating immune complexes were detectable in 80% of serum from patients with dengue haemorrhagic fever. The immune complexes were detected for the first time on day two after the onset of the fever. The amount of complexes reached the maximum value on day 4 or 5 after onset, or when the patients developed shock or subsidence of fever, after which the complexes decreased in number. The number of complexes also correlated well with the clinical grading (severity) of the disease, i.e. the maximum amount was shown in grade III. These complexes may play a part in the pathogenesis of this disease.

56 citations


Journal ArticleDOI
TL;DR: By the direct immunofluorescent technic, dengue antigen, human immunoglobulins, and beta 1C globulin were detectable on the surfaces of platelet suspensions from 48% of patients with d Dengue hemorrhagic fever.
Abstract: By the direct immunofluorescent technic, dengue antigen, human immunoglobulins, and β1C globulin were detectable on the surfaces of platelet suspensions from 48% of patients with dengue hemorrhagic fever. The percentages of positive-staining platelets were not related to the severity of thrombocytopenia, which was marked on the day after the patient developed shock or subsidence of fever. It is suggested that an immunologic mechanism is one of the factors associated with the thrombocytopenia caused by increased platelet destruction.

55 citations


Journal Article
TL;DR: With good cooperation between the hospital and the virology laboratory, new serotypes and possibly even new strains of virus can be identified before the onset of epidemic activity, which may make it possible to prevent major epidemics in the future.
Abstract: A dengue haemorrhagic fever surveillance system in Indonesia, based on virological and clinical observations, is described. The system uses the mosquito inoculation technique for virus isolation and is simple, economical, and well suited for endemic areas where support and facilities are limited. The data suggest that with good cooperation between the hospital and the virology laboratory, new serotypes and possibly even new strains of virus can be identified before the onset of epidemic activity. This type of virological surveillance may make it possible to prevent major epidemics in the future.

52 citations


Journal ArticleDOI
TL;DR: Dengue immunoglobulin M antibodies were demonstrated in an infant suspected of having a recent dengue infection by using the enzyme-linked immunosorbent assay.
Abstract: An enzyme-linked immunosorbent assay for the detection of antibodies to dengue virus is described. This method correlates well with a hemagglutination inhibition technique. The enzyme-linked immunosorbent assay can also be specific for human immunoglobulin M antibodies when a mu-chain-specific antiglobulin-enzyme conjugate and fractionated serum are employed. By using this technique, dengue immunoglobulin M antibodies were demonstrated in an infant suspected of having a recent dengue infection.

Journal ArticleDOI
TL;DR: Clinical observations were made on 95 serologically or virologically confirmed dengue fever cases during an epidemic in a rural area of Indonesia in December 1976, and the data suggest that one, and possibly two, of the fatal cases with virus isolation were primary infections, based on the results of hemagglutination-inhibition test using all four d Dengue antigens.
Abstract: Clinical observations were made on 95 serologically or virologically confirmed dengue fever cases during an epidemic in a rural area of Indonesia in December 1976. The age distribution was similar to that observed in patients with dengue hemorrhagic fever in Jakarta, a highly endemic urban area. The observed disease ranged in severity from undifferentiated fever to shock and death. The majority of patients had acute onset of fever with nausea, vomiting, headache, and abdominal pain. Hepatomegaly was observed in only 19% of the patients. A positive tourniquet test was the most frequently observed hemorrhagic manifestation, but epistaxis was observed in 20% and hematemesis in 6% of the patients. Dengue shock syndrome was observed in 37% of the patients. There were four deaths, three of which were confirmed as due to dengue infection by virus isolation. The data suggest that one, and possibly two, of the fatal cases with virus isolation were primary infections, based on the results of hemagglutination-inhibition test using all four dengue antigens.

Journal ArticleDOI
Akira Igarashi1
23 Aug 1979-Nature
TL;DR: In experiments with A. albopictus (Singh) cells persistently infected with d Dengue viruses, it is shown that such cultures produce ts viruses and become resistant to all the types of dengue viruses.
Abstract: DENGUE VIRUSES, which have four serotypes, belong to the genus flavivirus of Togaviridae and are transmitted by mosquitoes such as Aedes aegypti or Aedes albopictus. Human infection with dengue viruses is manifested by disease varying in severity from mild undiflferentiated fever to grave haemorrhagic fever, which is widespread in Southeast Asia1–3. Persistently infected cultures can be established when cultured mosquito cells are infected with Togaviridae, either alphaviruses or flavi viruses4–7. Analysis of mosquito cells persistently infected with alphaviruses has shown characteristics such as the generation of small-plaque and temperature-sensitive (ts) viruses7–9, and resistance to superinfections with the homologous but not the heterologous viruses6,10. In contrast, little is known about mosquito cells persistently infected with flavi viruses4,11,12. Here, in experiments with A. albopictus (Singh) cells persistently infected with dengue viruses, I show that such cultures produce ts viruses and become resistant to all the types of dengue viruses.

Journal ArticleDOI
TL;DR: Aedes albopictus mosquitoes were fed a blood suspension containing dengue-2 virus and tested by the fluorescent antibody technique, with the purpose of demonstrating the development of d Dengue virus.
Abstract: Aedes albopictus mosquitoes were fed a blood suspension containing dengue-2 virus. Lots of these mosquitoes were collected every other day for 3 weeks and tested by the fluorescent antibody technique, with the purpose of demonstrating the development of dengue virus. Two days after ingestion of an infectious blood meal, dengue virus antigen was limited to the cells of the posterior midgut. The proventriculus, fat body, nervous system, ovariole sheath and small portions of the salivary glands displayed fluorescence by the 6th day after infection. After day 6, dengue antigen was found disseminated in numerous tissues. The amount of demonstrable antigen and intensity of Huorescence was most marked in structures of the nervous system. Viral antigen was not consistently and uniformly demonstrated in the salivary glands, and qualitatively the type of fluorescence was different from that of other infected tissues. Dengue antigen was not demonstrated in eggs or the spermatheca.

Journal ArticleDOI
TL;DR: During outbreaks of dengue fever in the Caribbean in 1977 and 1978 a continuous cell line derived from Aedes pseudoscutellaris was successfully used for the isolation of d Dengue virus strains from acute human sera, found to be much more sensitive than conventional mouse inoculation.
Abstract: During outbreaks of dengue fever in the Caribbean in 1977 and 1978 a continuous cell line derived from Aedes pseudoscutellaris was successfully used for the isolation of dengue virus strains from acute human sera. 238 strains were isolated and culture fluid was successfully used as antigen for the identification of several strains. The isolates all produced a marked syncytial cytopathic effect often visible as early as four days after inoculation. The method was successfully employed in the field where, because of their low optimal incubation temperature, the cells suffered no ill effects under ambient conditions. The isolation method was found to be much more sensitive than conventional mouse inoculation.

Journal Article
TL;DR: A pyrogen active in ferrets with the characteristics of leucocyte (endogenous) pyrogen was produced by incubating influenza virus with ferret peripheral phagocytes in vitro and many of the cells were shown by fluorescent antibody to have interacted with influenza virus.
Abstract: Intranasal infection of ferrets with a virulent Clone (7a) of the recombinant influenza virus A/PR/8/34—A/England/939/69 (H3N2) produced a fever approximately 24 h in duration beginning about 29 h after infection. The origin of this fever has been investigated as an indication of what might happen in influenza in man. The systemic production of fever by virus interaction with phagocytes in the reticuloendothelial system appeared unlikely because insufficient virus escaped into the bloodstream. Ten half-hourly i.v. injections of 108 50%0 Egg-Bit Infectious Doses (EBID50) of virus were needed to produce a fever of short duration (3-8 h). Yet, after the intranasal infection, which results in the 24 h fever, the total virus content in the nasal mucosa was less than 108 EBID50 before the onset of fever and only reached 108.5 EBID50 for 4 h during fever. Also, just before or during the fever produced by intranasal infection, influenza virus antigens could not be detected by fluorescent antibody in the spleens of the animals but were detected in animals receiving a single bloodstream injection of 108 EBID50 of virus. Fever is more likely to result from release of leucocyte pyrogen by virus-phagocyte interaction in the upper respiratory tract. A pyrogen active in ferrets with the characteristics of leucocyte (endogenous) pyrogen was produced by incubating influenza virus with ferret peripheral phagocytes in vitro. A pyrogen with similar properties was released by incubation of nasal inflammatory cells collected from infected febrile ferrets and many of the cells were shown by fluorescent antibody to have interacted with influenza virus.

Journal Article
TL;DR: During the d Dengue outbreak which occurred in Reunion Island, one dengue type 2 strain was isolated at Institute Pasteur in Madagascar.
Abstract: During the dengue outbreak which occurred in Reunion Island, one dengue type 2 strain was isolated at Institute Pasteur in Madagascar.

Journal ArticleDOI
TL;DR: A significant increase in numbers of atypical lymphocytes and B lymphocytes, and a decrease in T lymphocytes by comparison with normal controls was revealed in patients with dengue hemorrhagic fever.
Abstract: Eighty-eight specimens consisting of lymphocytes separated from peripheral blood samples from 76 patients with dengue hemorrhagic fever (DHF) were studied. The results revealed a significant increase in numbers of atypical lymphocytes and B lymphocytes, and a decrease in T lymphocytes by comparison with normal controls. Anti-T lymphocyte antibody was also detected in the serum of all patients with DHF. The greatest increments and decrements of the above were noted on the day of shock of subsidence of fever.


Journal ArticleDOI
TL;DR: The demonstration of a dengue maternal infection-enhancing factor in human cord blood from d Dengue-immune mothers supports the hypothesis that severe primary dengued hemorrhagic fever with shock seen in Bangkok infants is related to maternal immune status.
Abstract: 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.


01 Mar 1979
TL;DR: The sensitivity of the mosquito inoculation technique for isolation of dengue viruses is discussed and d Dengue 3 was the predominant virus isolated.
Abstract: Virus isolations from dengue hemorrhagic fever patients in Indonesia are reported from 1975 to 1978. All 4 dengue serotypes were endemic in Jakarta, but dengue 3 was the predominant virus isolated. This type was also the most frequently isolated virus from patients outside Jakarta and had the widest distribution in Indonesia. The sensitivity of the mosquito inoculation technique for isolation of dengue viruses is discussed.

Journal Article
TL;DR: The buffy coat diagnosis of secondary DHF was correct in 94.2% of cases as early as the third day of fever, and the observation of many transformed lymphocytes in the peripheral blood of DHF patients also offer some insight into the pathogenesis of this condition.
Abstract: Examination of the buffy coat preparation is a simple, rapid diagnostic aid for the early diagnosis of dengue hemorrhagic fever (DHF). The presence of many transformed lymphocytes, usually 20-50 per cent during the first few days of fever is a unique finding especially during a secondary infection. Similar findings are absent during the early phase of illness in other viral infections. The buffy coat appearance in DHF is also clearly different from those in patients with bacterial infections, which show many polymorphonuclear leukocytes containing toxic granules and vacuoles. The early buffy coat diagnosis in 320 cases of DHF correlated well with the later serologic diagnosis. The buffy coat diagnosis of secondary DHF was correct in 94.2% of cases as early as the third day of fever. This technique has proven to be clinically useful for early screening test of secondary DHF in Southeast Asian countries. The observation of many transformed lymphocytes in the peripheral blood of DHF patients also offer some insight into the pathogenesis of this condition.



Journal ArticleDOI
Alfred S. Evans1, A V Wells, F Ramsay, P Drabkin1, K Palmer1 
TL;DR: A follow-up study of poliomyelitis, rubella, and dengue antibodies has been made in light of results obtained in a 1972 health and serological survey in Barbados.
Abstract: A follow-up study of poliomyelitis, rubella, and dengue antibodies has been made in light of results obtained in a 1972 health and serological survey in Barbados, W.I. Poliomyelitis antibody neutralization tests performed on sera from 307 children under age 15 using overnight serum/virus mixtures on microtiter plates at low serum dilutions revealed the absence of polio antibody at 1:2 dilution in 13.7% for type 1, 6.5% for type 2, and 14.3% for type 3 virus. A significant correlation of the presence or absence of poliomyelitis antibody to types 2 and 3 was seen with the response to immunization histories. Forty-three of 49 girls (88%) given rubella vaccine (RA 27/3) in 1972 had demonstrable haemagglutination-inhibition antibody 4 years later. Neutralization tests for dengue antibody confirmed the results of the complement-fixation tests and indicated that type 2 was probably the sole infecting strain.


Journal ArticleDOI
TL;DR: Mice infected with Dengue virus show a depressed immune response to lipopolysaccharide (LPS), a helper T-cell-independent antigen, when LPS was administered on day 0, 6 and 12 post infection.
Abstract: Mice infected with Dengue virus show a depressed immune response to lipopolysaccharide (LPS), a helper T-cell-independent antigen, when LPS was administered on day 0, 6 and 12 post infection. Mice injected with inactivated virus failed to show immunosuppression.

Journal Article
TL;DR: Isolation of tick-borne encephalitis virus and detection of specific serum antibodies in humans, animals and migratory birds demonstrate its presence on the territory of Romania, drawing attention to the possibility of human infections with arboviruses belonging to Kemerovo, California and Bunyavirus groups.
Abstract: The results obtained in the Institute of Virology by the study of arboviruses in Romania are reviewed. Isolation of tick-borne encephalitis virus and detection of specific serum antibodies in humans, animals and migratory birds demonstrate its presence on the territory of Romania. Serum antibodies could also be detected to other three flaviviruses (West Nile, Ntaya, dengue types 1, 2, 3), though none of them could be isolated in our country. However, isolation of Kemerovo and Tahyna viruses and detection of antibodies to these viruses as well as to Calovo virus draw attention to the possibility of human infections with arboviruses belonging to Kemerovo, California and Bunyavirus groups.

Journal ArticleDOI
TL;DR: The correlation between the concentration of virus injected and the performance of the mice was confirmed by the extent of lesions found by histologic study: animals that had anatomic lesions after surviving encephalitic infection showed abnormal behavior.
Abstract: The behavior of 1,072 mice that had recovered from encephalitic infection with intracerebrally injected yellow fever virus 17D and of 216 normal mice was tested in a maze and on a horizontal rod rotating around its axle. Infected animals needed more time (average, 8.90 min) to find their food in a maze than did normal animals (average, 4.37 min). Infected mice were able to stay on the rotating rod for a shorter time (average, 6.4 seconds) than were normal animals (average, 9.0 seconds). The correlation between the concentration of virus injected and the performance of the mice was confirmed by the extent of lesions found by histologic study: animals that had anatomic lesions after surviving encephalitic infection showed abnormal behavior.