Showing papers on "Dengue fever published in 1988"

Pathogenesis of dengue: challenges to molecular biology

Abstract: Dengue viruses occur as four antigenically related but distinct serotypes transmitted to humans by Aedes aegypti mosquitoes. These viruses generally cause a benign syndrome, dengue fever, in the American and African tropics, and a severe syndrome, dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), in Southeast Asian children. This severe syndrome, which recently has also been identified in children infected with the virus in Puerto Rico, is characterized by increased vascular permeability and abnormal hemostasis. It occurs in infants less than 1 year of age born to dengue-immune mothers and in children 1 year and older who are immune to one serotype of dengue virus and are experiencing infection with a second serotype. Dengue viruses replicate in cells of mononuclear phagocyte lineage, and subneutralizing concentrations of dengue antibody enhance dengue virus infection in these cells. This antibody-dependent enhancement of infection regulates dengue disease in human beings, although disease severity may also be controlled genetically, possibly by permitting and restricting the growth of virus in monocytes. Monoclonal antibodies show heterogeneous distribution of antigenic epitopes on dengue viruses. These epitopes serve to regulate disease: when antibodies to shared antigens partially neutralize heterotypic virus, infection and disease are dampened; enhancing antibodies alone result in heightened disease response. Further knowledge of the structure of dengue genomes should permit rapid advances in understanding the pathogenetic mechanisms of dengue.

A prospective study of dengue infections in Bangkok.

Abstract: Dengue infections were prospectively studied among 4- to 16-year-old students at a Bangkok school. Blood samples were obtained from 1,757 students in June 1980, before the dengue season, and in January 1981, after the season, and tested for dengue antibodies by the hemagglutination inhibition method. Classrooms were monitored daily for school absences. Fifty percent of the children had antibodies to, and were presumably immune to, at least 1 dengue serotype by the age of 7 years. Most (90/103, 87%) students who became infected by dengue viruses during the study period were either asymptomatic or minimally symptomatic (absent only 1 day). Most (7/13, 53%) of the symptomatic dengue infections (absent with fever for greater than or equal to 2 days) were clinically recognized as cases of dengue hemorrhagic fever which required hospitalization. None of 47 primary dengue infections required hospitalization, whereas 7 of 56 secondary infections did (P = 0.012). Preexistent dengue immunity, as detected by conventional serologic techniques, was a significant (odds ratio greater than or equal to 6.5) risk factor for development of dengue hemorrhagic fever.

Evidence that maternal dengue antibodies are important in the development of dengue hemorrhagic fever in infants.

Abstract: To establish the role of maternal dengue-specific antibodies in the development of dengue hemorrhagic fever and dengue shock syndrome caused by dengue 2 virus in infants, we examined sera from mothers of infants and toddlers with dengue hemorrhagic fever or dengue shock syndrome and mothers of infants with pyrexia of unknown origin. The mean titers of hemagglutination inhibition, neutralization, and infection-enhancing activities against dengue 2 virus were not statistically different among the three groups. However, among infants who developed dengue hemorrhagic fever/dengue shock syndrome there was a strong correlation between the mothers' dengue 2 neutralizing titers and infant age at the time of onset of severe illness, where no such correlation was found among the other two groups. Furthermore, the actual age at which dengue hemorrhagic fever/dengue shock syndrome occurred in each infant correlated with the age at which maximum enhancing activity for dengue 2 infection in mononuclear phagocytes was predicted. This critical time for the occurrence of dengue hemorrhagic fever/dengue shock syndrome was observed to be approximately 2 months after the time calculated for maternal dengue 2 neutralizing antibodies to degrade below a protective level. In addition, sera of mothers of infants with dengue hemorrhagic fever/dengue shock syndrome enhanced dengue 2 virus infection to a slightly greater degree than did sera from mothers of infants with pyrexia of unknown origin and toddlers with dengue hemorrhagic fever/dengue shock syndrome. These data are consistent with the hypothesis that maternal dengue antibodies play a dual role by first protecting and later increasing the risk of development of dengue hemorrhagic fever/dengue shock syndrome in infants who become infected by dengue 2 virus.

Protection against Japanese Encephalitis by Inactivated Vaccines

Abstract: Encephalitis caused by Japanese encephalitis virus occurs in annual epidemics throughout Asia, making it the principal cause of epidemic viral encephalitis in the world. No currently available vaccine has demonstrated efficacy in preventing this disease in a controlled trial. We performed a placebo-controlled, blinded, randomized trial in a northern Thai province, with two doses of monovalent (Nakayama strain) or bivalent (Nakayama plus Beijing strains) inactivated, purified Japanese encephalitis vaccine made from whole virus derived from mouse brain. We examined the effect of these vaccines on the incidence and severity of Japanese encephalitis and dengue hemorrhagic fever, a disease caused by a closely related flavivirus. Between November 1984 and March 1985, 65,224 children received two doses of monovalent Japanese encephalitis vaccine (n = 21,628), bivalent Japanese encephalitis vaccine (n = 22,080), or tetanus toxoid placebo (n = 21,516), with only minor side effects. The cumulative attack rate for encephalitis due to Japanese encephalitis virus was 51 per 100,000 in the placebo group and 5 per 100,000 in each vaccine group. The efficacy in both vaccine groups combined was 91 percent (95 percent confidence interval, 70 to 97 percent). Attack rates for dengue hemorrhagic fever declined, but not significantly. The severity of cases of dengue was also reduced. We conclude that two doses of inactivated Japanese encephalitis vaccine, either monovalent or bivalent, protect against encephalitis due to Japanese encephalitis virus and may have a limited beneficial effect on the severity of dengue hemorrhagic fever.

Gamma interferon augments Fc gamma receptor-mediated dengue virus infection of human monocytic cells.

Abstract: It has been reported that anti-dengue antibodies at subneutralizing concentrations augment dengue virus infection of monocytic cells. This is due to the increased uptake of dengue virus in the form of virus-antibody complexes by cells via Fc gamma receptors. We analyzed the effects of recombinant human gamma interferon (rIFN-gamma) on dengue virus infection of human monocytic cells. U937 cells, a human monocytic cell line, were infected with dengue virus in the form of virus-antibody complexes after rIFN-gamma treatment. Pretreatment of U937 cells with rIFN-gamma resulted in a significant increase in the number of dengue virus-infected cells and in the yield of infectious virus. rIFN-gamma did not augment dengue virus infection when cells were infected with virus in the absence of anti-dengue antibodies. Gamma interferon (IFN-gamma) produced by peripheral blood lymphocytes from dengue-immune donors after in vitro stimulation with dengue antigens also augmented dengue virus infection of U937 cells. IFN-gamma did not augment dengue virus infections when cells were infected with virus in the presence of F(ab')2 prepared from anti-dengue immunoglobulin G. Human immunoglobulin inhibited IFN-gamma-induced augmentation. IFN-gamma increased the number of Fc gamma receptors on U937 cells. The increase in the percentage of dengue antigen-positive cells correlated with the increase in the number of Fc gamma receptors after rIFN-gamma treatment. These results indicate that IFN-gamma-induced augmentation of dengue virus infection is Fc gamma receptor mediated. Based on these results we conclude that IFN-gamma increases the number of Fc gamma receptors and that this leads to an augmented uptake of dengue virus in the form of dengue virus-antibody complexes, which results in augmented dengue virus infection.

Immunization of mice with dengue structural proteins and nonstructural protein NS1 expressed by baculovirus recombinant induces resistance to dengue virus encephalitis.

Abstract: We have constructed a recombinant baculovirus containing a 4.0-kilobase dengue virus cDNA sequence that codes for the three virus structural proteins, capsid (C) protein, premembrane (PreM) protein, and envelope glycoprotein (E), and nonstructural proteins NS1 and NS2a. Infection of cultured Spodoptera frugiperda cells with this recombinant virus resulted in the production of E and NS1 proteins that were similar in size to the corresponding viral proteins expressed in dengue virus-infected simian cells. Other dengue virus-encoded proteins such as PreM and C were also synthesized. Rabbits immunized with the dengue virus protein products of the recombinant virus developed antibodies to PreM, E, and NS1, although the titers were low, especially to PreM and E. Nevertheless, the dengue virus antigens produced by the recombinant virus induced resistance in mice to fatal dengue encephalitis.

Vector competence of a Houston, Texas strain of Aedes albopictus for Rift Valley fever virus.

Abstract: : The recent introduction of Aedes albopictus into the Americas has led to concern that this mosquito might serve as a vector of both native as well as exotic viruses Experimental and field data indicate that this species is capable of transmitting chikungunya, Japanese encephalitis, yellow fever, West Nile, Ross River, and all 4 serotypes of dengue viruses, as well as St Louis encephalitis and western equine encephalitis viruses We evaluated the potential of the F3 generation of a Houston, Texas strain of Ae albopictus to transmit Rift Valley fever (RVF) virus Female mosquitoes, 5 to 10 days old reared at 26 C with a 16:8 L:D photoperiod, were allowed to feed on an anesthetized hamster that had been inoculated with RVF virus 24 hours previously Recovery of virus from the body, but not the legs, indicated that viral infection was limited to the midgut and had not disseminated to the hemocoel, while recovery of virus from both legs and body indicated that the mosquito had a disseminated infection Ae albopictus should be considered a potential vector of RVR virus, should it be introduced into the southern United States Reprints

Unusual clinical manifestations of dengue virus infection.

Abstract: Four recent cases of dengue fever with severe, unusual clinical manifestations are described Two of these cases had features of fulminant hepatitis and encephalopathy; one of these cases was fatal The two remaining cases showed hepatitis with renal impairment The significance and importance of these unusual manifestations of dengue disease are discussed

Virological study of a dengue type 1 epidemic at Rio de Janeiro

Abstract: A dengue outbreak started in March, 1986 in Rio de Janeiro and spread very rapidly to other parts of the country. The great majority of cases presented classical dengue fever but there was one fatal case, confirmed by virus isolation. Dengue type 1 strains were isolated from patients and vectors (Aedes aegypti) in the area by cultivation in A. albopictus C6/36 cell line. The cytopathic effect (CPE) was studied by electron microscopy. An IgM capture test (MAC-ELISA) was applied with clear and reproducible results for diagnosis and evaluation of virus circulation; IgM antibodies appeared soon after start of clinical disease, and persisted for about 90 days in most patients. The test was type-specific in about 50% of the patients but high levels of heterologous response for type 3 were observed. An overall isolation rate of 46.8% (813 virus strains out of 1734 specimens) was recorded. The IgM test increased the number of confirmed cases to 58.2% (1479 out of 2451 suspected cases). The importance of laboratory diagnosis in all regions where the vectors are present is emphasized.

Dengue infections in the Philippines: clinical and virological findings in 517 hospitalized patients.

Abstract: From May 1983 to January 1984, 517 patients with laboratory confirmed dengue were studied at a hospital in Manila. Secondary dengue infections were diagnosed in 78% of these cases. Peak admission (28%) occurred towards the end of the rainy season in November. Most patients (78%) were less than 15 years old but only 3 were infants. Although some type of hemorrhagic finding occurred in 460 cases (89%), only 110 were classified as dengue hemorrhagic fever and the remainder as dengue fever with hemorrhagic manifestations. The clinical course was usually mild. Gastrointestinal bleeding was present in 65 cases, but only 2 patients developed shock. No fatalities occurred. Dengue 2 was the predominant serotype with 53 isolates, followed by dengue 1 with 48 isolates, dengue 3 with 39 isolates, and dengue 4 with only 8 isolates. Dengue 2 was the only serotype with more isolates from sera with a homologous HI antibody titer greater than 1:20 (57%) than from sera with a homologous HI titer less than or equal to 1:20 (43%). In contrast, most of the dengue 1 isolates (63%) were from sera with a homologous HI antibody titer less than 1:10, and this serotype was strongly associated with primary infections. This study shows that dengue infections remain an important cause of pediatric hospitalization in the Philippines; however, the occurrence of life-threatening dengue hemorrhagic fever as has been described in several other large urban areas of Southeast Asia appears to be rare.

Production of interferon alpha by dengue virus-infected human monocytes.

Abstract: Summary Human monocytes appear to be very important in the pathogenesis of dengue infection. They are thought to be the most active sites of virus replication during dengue infection. We have analysed interferon (IFN) production by dengue virus from peripheral blood mononuclear cells (PBMC). IFN activity was first detected at 12 h after infection of monocytes and reached a maximum level by 48 h. Non-adherent PBMC depleted of monocytes did not produce detectable levels of IFN, and did not contain dengue antigen-positive cells after exposure to dengue virus. The IFN produced was characterized as IFN-α by neutralization tests using specific antisera to HuIFN-α, HuIFN-β and HuIFN-γ, and by radioimmunoassay. The culture fluids of dengue virus-infected monocytes, which contained IFN-α, were able to inhibit infection of human monocytes by dengue virus. These results suggest that IFN-α produced by dengue virus-infected monocytes may play an important role in controlling primary dengue virus infection.

Dengue 2 virus envelope protein expressed by a recombinant vaccinia virus fails to protect monkeys against dengue.

Abstract: A cDNA copy of the dengue (DEN) 2 virus genome region encoding the virion capsid, membrane and envelope structural proteins has been inserted into vaccinia virus (VV) DNA under the control of its 11K late promoter. The DEN-2 envelope protein was expressed and processed in cells infected with the VV recombinant (VV/D2S). No DEN-2 virus antibody response was detected in mice, hamsters or monkeys vaccinated with VV/D2S. Furthermore, a viraemia was observed in recombinant-vaccinated monkeys after challenge with infectious DEN-2 virus.

Vertical transmission of dengue viruses by Aedes mediovittatus.

Abstract: Aedes mediovittatus, a forest and peridomestic mosquito found in the Caribbean area, has previously been shown to be highly susceptible to oral infection with dengue viruses in the laboratory. In the present study, the species was found to transmit all four dengue serotypes vertically (i.e., from one generation to another) at rates much higher than any observed previously for flaviviruses in mosquitoes. Vertical transmission rates (the percentage of parent females transmitting to one or more progeny) ranged up to 95%. Filial infection rates (the percentage of infected progeny) varied widely by family but rates greater than or equal to 20% for individual families were not uncommon. Since Ae. mediovittatus feeds readily on humans and is relatively abundant, there is no apparent reason why it would not serve as a vector of dengue. If it does, vertical transmission of the virus in this species would contribute to the maintenance of viral endemicity.

Pathogenesis of dengue.

Abstract: Dengue, which is caused by four antigenically different flaviviruses and is transmitted by mosquitoes, affects as many as 100 million people per year.

Natural killer cells in dengue hemorrhagic fever/dengue shock syndrome.

Abstract: Natural killer (NK) cell activity against K-562 target cells and HNK-1+ cell levels were serially determined in peripheral blood of 62 Thai children with dengue hemorrhagic fever/dengue shock syndrome aged 4-12 years and 59 age-matched normal controls. The studies were performed on febrile stage, 1st and 2nd day of subsidence of fever (shock stage), 3rd and 4th day of subsidence of fever (early convalescent stage) and once again on the late convalescent stage (approximately 14-18 days after subsidence of fever). The study revealed that during the course of disease the NK cell activity was not changed significantly from the normal controls. In contrast, the levels of HNK-1+ cells, which exhibited almost all NK and killer cell functional activities, were significantly decreased in the febrile and the shock stages and were normal in the early and late convalescent stages. The NK cell activity, on the per-cell basis, was significantly increased in the early disease stage when compared to that of the later period of the disease and of the normal controls. The study also revealed that patients with grade III of disease severity exhibited significantly more NK cell functional activities per cell than grade II on febrile stage and the first day of shock. These results suggest that natural killer cells were active in defense against dengue viral infection and might play some role in the pathogenesis of dengue hemorrhagic fever/dengue shock syndrome. Their functions might also determine the severity of the disease.

Heterologous flavivirus infection-enhancing antibodies in sera of Nigerians.

Abstract: Human sera collected from Nigerians were examined for plaque reduction neutralizing and infection-enhancing antibodies against dengue 2, yellow fever, and West Nile viruses. Neutralization tests showed that 17 of 19 sera contained flavivirus neutralizing antibody; 11 were positive to all 3 viruses, 5 to dengue and yellow fever, and 1 to dengue virus only. Two sera had no detectable neutralizing antibody to any of the flaviviruses. Enhancement assays showed that 17 flavivirus neutralizing antibody-positive sera contained infection-enhancing antibodies to dengue 2, and 16 had antibody to yellow fever. Although 11 sera were positive for West Nile neutralizing antibody, 17 enhanced this virus. Heterologous infection-enhancing antibody titers were lower than the homologous ones. Broadly reacting sera and those with high neutralizing antibody titers produced the highest infection-enhancing antibody titers.

[Aedes aegypti (L.): importance of its bioecology in the transmission of dengue and other arboviruses. I].

Abstract: The bioecological parameters which are of special importance in the epidemiology of Dengue, Yellow Fever, and other arboviruses are discussed. Three levels are retained: the nature of Aedes aegypti-man contacts, the susceptibility of the mosquito to the pathogen and multiplication of the latter, and the transmission. The trophic preferences, the density variations, the daily survival rate, the egg diapause, and man influences are the main vector-dependent ecological factors. Temperature and genetical nature of viral and mosquito strains are particularly important in susceptibility and multiplication studies. Efficacy of the oral transmission is also temperature-dependent and mainly genetically determined. The true natural role of transovarial transmission is not yet well understood. Thus, the breaking up and/or prevention of epidemics would be possible only with a thorough knowledge of the relation between the above biological factors and the epidemiological situation. A list is provided of the naturally or experimentally Aedes aegypti transmitted arboviruses (103), protozoans (5) and filaria (20).

Dengue haemorrhagic fever and Japanese B encephalitis in Indonesia.

Abstract: Dengue haemorrhagic fever (DHF) was first recognized in Indonesia in the cities of Jakarta and Surabaya in 1968, 15 years after its recognition in the Philippines. During the 1968 outbreak, a total of 58 clinical cases with 24 deaths were reported. The number of reported cases since then has increased sharply, with the highest number of cases recorded in the years 1973 (10,189 cases), 1983 (13,668 cases), and 1985 (13,588 cases). Outbreaks of the disease have spread to involve most of the major urban areas, as well as some of the rural areas. In 1985, the disease had spread to 26 of 27 Provinces and 160 of 300 regencies of municipalities. At present, the disease is endemic in many large cities and small towns. Interestingly, DHF has not been reported in some cities, even though dengue virus transmission rates in those cities are high. The epidemic pattern of DHF for the country as a whole has become irregular. Since 1982, the intensity and spread of DHF has created an increasing public health problem in Indonesia, particularly in Java where 60% of the total population of the country resides. Java contributed about 71% of all cases occurring in the country in 1982, 84% in 1983, and 91% in 1984. The peak monthly incidence of DHF was frequently reported during October through April, months which coincide with the rainy season. The morbidity rate for Indonesia, estimated from reported cases over five years (1981-1985), ranged between 3.39 to 8.65 per 100,000 population. The overall case fatality rate has steadily declined from 41.3% in 1968 to 3% in 1984.(ABSTRACT TRUNCATED AT 250 WORDS)

Viral hemorrhagic fever

Abstract: REPORTING INFORMATION • Class A: Report immediately via telephone the case or suspected case and/or a positive laboratory result to the local public health department where the patient resides. If patient residence is unknown, report immediately via telephone to the local public health department in which the reporting health care provider or laboratory is located. Local health departments should report immediately via telephone the case or suspected case and/or a positive laboratory result to the Ohio Department of Health (ODH). • Reporting Form(s) and/or Mechanism: o Immediately via telephone. o For local health departments, cases should also be entered into the Ohio Disease Reporting System (ODRS) within 24 hours of the initial telephone report to the ODH. • Key fields for ODRS reporting include: import status (whether the infection was travel-associated or Ohio-acquired), date of illness onset, and all the fields in the Epidemiology module.

Dengue Epidemics on the Pacific Coast of Mexico

Abstract: Dengue epidemics in three Mexican cities were investigated with retrospective surveys and virus isolations from acute cases. These epidemics were part of the continuing extension of dengue in Mexico since 1978 after 15 years without transmission. Serotype 1 dengue infection predominated in all epidemics, but in one city, type 2 strains were also isolated. The following findings were consistent in all three cities: 1) illness history provided evidence of presence of infection months before the epidemic became evident, 2) there was a very sharp and progressive increase of dengue illness attack rates by age, 3) there were no interpretable relationships between illness and the presence of different types of breeding sights in the home, 4) socioeconomic status was strongly negatively related to illness, and 5) geographical factors not related to the other measured variables had a strong effect on illness rates reflecting the focality of transmission. In addition, there was evidence of a strong protective effect against illness by the use of mosquito netting or the presence of screens on houses, but these relationships were not universal to all three cities.

Togaviridae and Flaviviridae: The Alphavirases and Flaviviruses

Abstract: Diseases: Yellow fever, dengue, St. Louis encephalitis, Japanese encephalitis, Wes- selsbron, tick-borne encephalitis, louping ill, Kyasanur Forest disease, other tick- borne hemorrhagic fevers, Murray Valley encephalitis, Rocio encephalitis, equine encephalitides (eastern, western, Venezuelan), chikungunya, o’nyong-nyong, Ross River, Mayaro, Sindbis, Ockelbo.

Kinetics of lymphocyte subpopulations in dengue hemorrhagic fever/dengue shock syndrome.

Abstract: A kinetic study of lymphocyte subpopulations was performed in 61 dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) patients aged 8 months to 12 years and in 59 age-matched normal controls. There were 36 patients in grade 2 and 25 patients in grade 3 of the disease severity. The studies were performed on febrile stage, the day of subsidence of fever or shock stage, 3 subsequent days after subsidence of fever or shock, and once on the recovery stage (approximately 14-18 days after subsidence of fever or shock). The study revealed that the absolute total lymphocytes, CD3+, CD4+, CD8+ and HNK-1+ cells were decreased on febrile stage and their lowest values were noted on the first day of subsidence of fever or shock, while B1+ cells were in the normal range. Thereafter, all lymphocyte subpopulations were increased. The total lymphocytes, B1+ and CD8+ cells were rapidly increased and were above normal value on day 2 after subsidence of fever or shock (early convalescence), then gradually declined to the normal range. In contrast, CD3+, CD4+ and HNK-1+ cells were increased gradually and reached their normal values on day 2 after subsidence of fever or shock. The T4:T8 ratio began to reverse on the day of subsidence of fever or shock, reached its peak on day 2 after shock and returned to normal ratio rapidly thereafter. Thus, the absolute lymphopenia on the day of shock was due to the decrement or T cells (both CD4+ and CD8+ cells) and HNK-1+ cells.(ABSTRACT TRUNCATED AT 250 WORDS)