scispace - formally typeset
Search or ask a question

Showing papers on "Dengue fever published in 1997"


Journal ArticleDOI
TL;DR: Control of dengue at the present time is dependent on control of the principal vector mosquito, A. aegypti, and indigenous transmission in the continental United States remains a public health concern.

895 citations


Journal ArticleDOI
14 Apr 1997-Virology
TL;DR: Phylogenetic analyses suggest that these genotypes of dengue type 2 virus originated in Southeast Asia and that they displaced the native, American genotype in at least four countries, and vaccination and other control efforts should therefore be directed at decreasing the transmission of these "virulent" genotypes.

676 citations


Journal ArticleDOI
TL;DR: Simple clinical and laboratory parameters are identified that help to identify children with DF or DHF, including plasma AST levels were higher in children who developed DHF than in those with DF.
Abstract: A prospective observational study was conducted to identify early indicators of acute dengue virus infection. Children with fever for <72 h without obvious cause were studied at hospitals in Bangkok and Kamphaeng Phet, Thailand, until resolution of fever. Of 172 evaluable subjects (91% of enrollees), 60 (35%) had dengue, including 32 with dengue fever (DF) and 28 with dengue hemorrhagic fever (DHF). At enrollment, children with dengue were more likely than children with other febrile illnesses (OFI) to report anorexia, nausea, and vomiting and to have a positive tourniquet test, and they had lower total white blood cell counts, absolute neutrophil and absolute monocyte counts, and higher plasma alanine and aspartate (AST) aminotransferase levels than children with OFI. Plasma AST levels were higher in children who developed DHF than in those with DF. These data identify simple clinical and laboratory parameters that help to identify children with DF or DHF.

642 citations



Journal ArticleDOI
TL;DR: This study demonstrates that all four serotypes of d Dengue virus can cause dengue hemorrhagic fever, that all dengu patients as defined by serology experience viremia during the febrile phase, and that as fever subsides, so does vireia.
Abstract: A multicenter effort was begun in 1994 to characterize the pathophysiology of dengue using a study design that minimized patient selection bias by offering enrollment to all children with undifferentiated fever for <72 h. In the first year, 189 children were enrolled (age range, 8 months to 14 years). Thirty-two percent of these children had dengue infections (60 volunteers). The percentage of children with a secondary dengue infection was 93%, with only 4 (7%) having a primary dengue infection. The virus isolation rate from the plasma of children with dengue was 98%. Viremia correlated highly with temperature. All four dengue virus serotypes were isolated at both study sites. This study demonstrates that all four serotypes of dengue virus can cause dengue hemorrhagic fever, that all dengue patients as defined by serology experience viremia during the febrile phase, and that as fever subsides, so does viremia.

436 citations


Journal ArticleDOI
TL;DR: The incidence of anamnestic dengue infections in DSS patients is found to be significantly higher than in the community from which they were drawn and a significantly higher risk of developing DSS following anAnamnestic infection (particularly with d Dengue 2 virus) than following a primary infection with any serotype.
Abstract: Despite a growing body of evidence predominantly, but not exclusively, from Thailand suggesting that the risk of developing dengue shock syndrome (DSS) is greatest following an anamnestic dengue infection, particularly if the most recent infection was with dengue 2 virus, there continues to be debate about the justification for these claims. This report describes a five-year, prospective study in two townships (suburbs) in Yangon (Rangoon) Myanmar (Burma) in which attempts were made to confirm the data from an earlier prospective study in Thailand and to address some of the criticism of earlier studies. This investigation found the incidence of anamnestic dengue infections in DSS patients to be significantly higher than in the community from which they were drawn and a significantly higher risk of developing DSS following an anamnestic infection (particularly with dengue 2 virus) than following a primary infection with any serotype.

386 citations


Journal ArticleDOI
TL;DR: It is argued that the existence of competitive exclusion in this system is product of the interplay between the host superinfection process and frequency-dependent (vector to host) contact rates.
Abstract: We study a system of differential equations that models the population dynamics of an SIR vector transmitted disease with two pathogen strains. This model arose from our study of the population dynamics of dengue fever. The dengue virus presents four serotypes each induces host immunity but only certain degree of cross-immunity to heterologous serotypes. Our model has been constructed to study both the epidemiological trends of the disease and conditions that permit coexistence in competing strains. Dengue is in the Americas an epidemic disease and our model reproduces this kind of dynamics. We consider two viral strains and temporary cross-immunity. Our analysis shows the existence of an unstable endemic state (‘saddle’ point) that produces a long transient behavior where both dengue serotypes cocirculate. Conditions for asymptotic stability of equilibria are discussed supported by numerical simulations. We argue that the existence of competitive exclusion in this system is product of the interplay between the host superinfection process and frequency-dependent (vector to host) contact rates.

343 citations


Journal ArticleDOI
14 Apr 1997-Virology
TL;DR: Although the NS3-250-Val mutation clearly affected virus replication in vitro, it was not a major determinant of attenuation for PDK-53 virus in suckling mice.

331 citations


Journal ArticleDOI
TL;DR: An initial attempt to quantify the influence of warming temperatures on the intensity and distribution of dengue transmission throughout the world using an expression of vectorial capacity modified to reflect the role of temperature on development and survival of the vector and virus is documented.
Abstract: The purpose of the present paper is to document an initial attempt to quantify the influence of warming temperatures on the intensity and distribution of dengue transmission throughout the world using an expression of vectorial capacity modified to reflect the role of temperature on development and survival of the vector and virus. We rearranged the traditional vectorial capacity expression (the mean number of potentially infective contacts made by a mosquito population per infectious person per unit time) to develop an equation for the critical density threshold, an estimate of the number of adult female vectors required to just maintain the virus in a susceptible human population. In this expression, temperature influences adult survival, the lengths of the gonotrophic cycle and the extrinsic incubation period of the virus in the vector, and vector size, a factor that indirectly influences the biting rate. Before making projections for warming scenarios of current climate plus 2 or 4 degrees C, we validate our technique by successfully comparing model projections and the observed spatial, temporal, and altitudinal distribution of dengue using current climate in five cities that are endemic or have had epidemics in the past. Our results indicate that the current warming projection of the International Council of Scientific Unions and the Intergovernmental Panel on Climate Change of 2 degrees C by the end of the next century can be expected to result in a potential increase in the latitudinal and altitudinal range of dengue; the potential duration of the transmission season will also increase in temperate locations as well. We discuss how an increase in temperature-related transmission intensity can be expected to lower the average ages of primary and secondary infections and thereby significantly increase the proportion of secondary infections occurring among infants and adolescents, the ages especially susceptible to dengue hemorrhagic fever and shock syndrome.

300 citations


01 Jan 1997
TL;DR: In Asian countries the disease continues to affect children predominantly although a marked increase in the number of DHF cases in people over 15 years old has been observed in the Philippines and Malaysia during recent years.
Abstract: About two-thirds of the world's population live in areas infested with dengue vectors, mainly Aedes aegypti. All four dengue viruses are circulating, sometimes simultaneously, in most of these areas. It is estimated that up to 80 million persons become infected annually although marked underreporting results in the notification of much smaller figures. Currently dengue is endemic in all continents except Europe and epidemic dengue haemorrhagic fever (DHF) occurs in Asia, the Americas and some Pacific islands. The incidence of DHF is much greater in the Asian countries than in other regions. In Asian countries the disease continues to affect children predominantly although a marked increase in the number of DHF cases in people over 15 years old has been observed in the Philippines and Malaysia during recent years. In the 1990's DHF has continued to show a higher incidence in South-East Asia, particularly in Viet Nam and Thailand which together account for more than two-thirds of the DHF cases reported in Asia. However, an increase in the number of reported cases has been noted in the Philippines, Lao People's Democratic Republic, Cambodia, Myanmar, Malaysia, India, Singapore and Sri Lanka during the period 1991-1995 as compared to the preceding 5-year period. In the Americas, the emergence of epidemic DHF occurred in 1981 almost 30 years after its appearance in Asia, and its incidence is showing a marked upward trend. In 1981 Cuba reported the first major outbreak of DHF in the Americas, during which a total of 344,203 cases of dengue were notified, including 10,312 severe cases and 158 deaths. The DHF Cuban epidemic was associated with a strain of dengue-2 virus and it occurred four years after dengue-1 had been introduced in the island causing epidemics of dengue fever. Prior to this event suspected cases of DHF or fatal dengue cases had been reported by five countries but only a few of them fulfilled the WHO criteria for diagnosis of DHF. The outbreak in Cuba is the most important event in the history of dengue in the Americas. Subsequently to it, in every year except 1983, confirmed or suspected cases of DHF have been reported in the Region. The second major outbreak in the Americas occurred in Venezuela in 1989 and since then this country has suffered epidemics of DHF every year. Between 1981 and 1996 a total of 42,246 cases of DHF and 582 deaths were reported by 25 countries in the Americas, 53% of which originated from Venezuela and 24% from Cuba. Colombia, Nicaragua and Mexico have each reported over 1,000 cases during the period 1992-1996. About 74% of the Colombian cases and 97% of the Mexican cases were reported during 1995-1996. A main cause of the emergence of DHF in the Americas was the failure of the hemispheric campaign to eradicate Aedes aegypti. Following a successful period that resulted in the elimination of the mosquito from 18 countries by 1962, the programme began to decline and as a result there was a progressive dissemination of the vector so that by 1997 with the exception of Canada, Chile and Bermuda, all countries in the Americas are infested. Other factors contributing to the emergence/re-emergence of dengue/DHF include the rapid growth and urbanization of populations in Latin America and the Caribbean, and increased travel of persons which facilitates dissemination of dengue viruses. Presently, all four dengue serotypes are circulating in the Americas, thus increasing the risk for DHF in this region.

284 citations


Journal ArticleDOI
TL;DR: These findings vis-à-vis the present endemic areas indicate that the increase in the epidemic potential of malaria and dengue transmission may be estimated at 12–27% and 31–47%, respectively, while in contrast, schistosomiasis transmission potential may be expected to exhibit a 11–17% decrease.
Abstract: Global assessment of the potential impacts of anthropogenically-induced climate change on vector-borne diseases suggests an increase in extent of the geographical areas susceptible to transmission of malarial Plasmodium parasites, dengue Flavivirus and Schistosoma worms. The transmission potential of the three associated vector-borne diseases studied is highly sensitive to climate changes on the periphery of the currently endemic areas and at higher altitudes within such areas. Our findings vis-a-vis the present endemic areas indicate that the increase in the epidemic potential of malaria and dengue transmission may be estimated at 12–27% and 31–47%, respectively, while in contrast, schistosomiasis transmission potential may be expected to exhibit a 11–17% decrease.

Journal ArticleDOI
TL;DR: It is shown that human umbilical vein endothelial cells become activated when exposed to culture fluids from dengue virus-infected peripheral blood monocytes, thus correlating with epidemiological evidence that prior immunity to d Dengue virus is a major risk factor for DHF.
Abstract: Although endothelial cells have been speculated to be a target in the pathogenesis of dengue hemorrhagic fever (DHF), there has been little evidence linking dengue virus infection to any alteration in endothelial cell function. In this study, we show that human umbilical vein endothelial cells become activated when exposed to culture fluids from dengue virus-infected peripheral blood monocytes. Maximum activation was achieved with culture fluids from monocytes in which virus infection was enhanced by the addition of dengue virus-immune serum, thus correlating with epidemiological evidence that prior immunity to dengue virus is a major risk factor for DHF. Activation was strongest for endothelial cell expression of VCAM-1 and ICAM-1. In contrast, activation of endothelial cell E-selectin expression appeared to be more transient, as indicated by its detection at 3 h, but not at 16 h, of treatment. Treatment of monocyte culture fluids with anti-tumor necrosis factor alpha (TNF-alpha) antibody largely abolished the activation effect (as measured by endothelial cell expression of ICAM-1), whereas treatment with IL-1beta receptor antagonist had a much smaller inhibitory effect on activation. Endothelial cells inoculated directly with dengue virus or with virus-antibody combinations were poorly infectable (compared to Vero cells or peripheral blood monocytes), and virus-inoculated endothelial cells showed no increased expression of VCAM-1, ICAM-1, or E-selectin. Taken together, the results strongly indicate that dengue virus can modulate endothelial cell function by an indirect route, in which a key intermediary is TNF-alpha released from virus-infected monocytes.

Journal ArticleDOI
TL;DR: Significant increases in the length of feeding activity in infected mosquitoes corresponded to virus infection in organs that are known to control or influence activities associated with blood feeding, which may contribute to the efficiency of Ae.
Abstract: In addition to heavily infecting the salivary glands of Aedes aegypti (L.) mosquitoes, dengue viruses produce a significant infection of the nervous system, involving the brain, Johnston's organ, compound eye, and thoracic and abdominal ganglion. To determine if dengue infection affects feeding behavior of Ae. aegypti we measured feeding times, counted the number of feeding delays or interruptions, and by in situ immunocytochemistry techniques determined the spatial and temporal distribution of dengue infections in females parenterally infected with dengue 3 virus. The mean of the total time required for feeding by infected mosquitoes was significantly longer than the time required by uninfected mosquitoes. Similarly, the mean of the time spent probing was significantly longer in infected mosquitoes than in uninfected mosquitoes when day after inoculation was considered. Significant increases in the length of feeding activity in infected mosquitoes corresponded to virus infection in organs that are known to control or influence activities associated with blood feeding. Sequential infections of the salivary glands (five days postinoculation [PI]), brain and compound eye (eight days PI), and Johnston's organ and midgut and abdominal ganglion (11 days PI) of most mosquitoes were observed. The increased time required by infected Ae. aegypti mosquitoes to acquire a blood meal may contribute to the efficiency of Ae. aegypti as a vector of dengue virus. Longer feeding periods are more likely to be interrupted by the host, which increases the chance that an infected mosquito will probe or feed on additional hosts.

Journal ArticleDOI
TL;DR: It is concluded that DHF may cause mild to moderate liver dysfunction in most cases; only some patients may suffer from acute liver failure leading to encephalopathy and death.

Journal Article
TL;DR: The results seem to indicate that infiltration of virus-infected macrophages could be one of the pathways by which viruses enter the brain in dengue encephalitis.
Abstract: Immunohistochemical procedure (avidin biotin peroxidase complex) was applied in formalin-fixed and paraffin-embedded tissues obtained from 5 fatal cases of dengue infection associated with encephalopathy. Dengue virus antigen was demonstrated in the cytoplasm of phagocytic mononuclear cells from liver, spleen, and lung. Moreover, dengue viral antigens were here, to our knowledge, first demonstrated in the central nervous system (CNS) and numerous immunolabelled cells were found in brain sections from 3 cases. Extended immunohistochemical studies carried out in 1 case showed virus-positive cells mostly located within Virchow Robin space of medium size and small veins, infiltrating the white and grey matter, and often situated close to neurons displaying apparent cytopathic features. Furthermore, immunostaining for CD68 antigens demonstrated that most CD68+ macrophages and dengue antigen-positive cells share similar morphology and localization, suggesting a unique identity for at least part of these cells. Since in dengue fever, virus replicates mostly in cells of macrophage lineage, our results seem to indicate that infiltration of virus-infected macrophages could be one of the pathways by which viruses enter the brain in dengue encephalitis. Whether bone marrow-derived infected macrophages and viral-free particles induce CSN lesions through immune, metabolic, and/or direct viral-induced mechanisms will be essential to better understand the pathogenesis and provide new therapeutic strategies for dengue-associated encephalitis. As the evidence of tissue damage was nonspecific, the detection of virus antigen by immunoperoxidase technique appeared to be highly reliable for dengue diagnosis.

Journal ArticleDOI
TL;DR: Mosquito collections were conducted during a dengue outbreak in Reynosa, Tamaulipas, Mexico, July‐December 1995, and it is the very first time Ae.albopictus males have been found infected with d Dengue virus in the wild.
Abstract: Mosquito collections were conducted during a dengue outbreak in Reynosa, Tamaulipas, Mexico, July-December 1995. A total of 6694 adult mosquitoes (four genera and nine species) were captured, of which 2986 (78.3% females and 21.7% males) were Aedes albopictus and 2339 (39.7% females and 60.3% males) were Ae.aegypti. These two species comprised 84.2% of the total collection. Specimens were grouped into pools, nearly 50% of them processed for detection of virus by cythopathic effect in C6-36 and VERO cell cultures and by haemagglutination test. Five pools gave positive haemagglutin-ation reactions and were examined by immunofluorescence using monoclonal antibodies to flavivirus and to dengue virus. One pool of ten Ae.albopictus males was positive for dengue virus: serotypes 2 and 3 were identified by serotype-specific monoclonal antibodies arid confirmed by RT-PCR. This is the first report of Ae.albopictus naturally infected with dengue virus in America. Also, it is the very first time Ae.albopictus males have been found infected with dengue virus in the wild.

Journal ArticleDOI
TL;DR: This report highlights not only the apparently rare occurrence of vertical transmission of dengue virus in humans but also the potential risk of death for infected neonates.
Abstract: Dengue, an important mosquito-borne flavivirus infection, is endemic in Southeast Asia. We describe two mothers who had acute dengue 4 and 8 days before the births of their infants. One mother had worsening of her proteinuric pregnancy-induced hypertension, liver dysfunction, and coagulopathy and required multiple transfusions of whole blood, platelets, and fresh frozen plasma. Her male infant was ill at birth, developed respiratory distress and a large uncontrollable left intracerebral hemorrhage, and died of multiorgan failure on day 6 of life. Dengue virus type 2 was isolated from the infant's blood, and IgM antibody specific to dengue virus was detected in the mother's blood. The second mother had a milder clinical course; she gave birth to a female infant who was thrombocytopenic at birth and had an uneventful hospitalization. Dengue virus type 2 was recovered from the mother's blood, and IgM antibody specific to dengue virus was detected in the infant's blood. This report highlights not only the apparently rare occurrence of vertical transmission of dengue virus in humans but also the potential risk of death for infected neonates.

Journal ArticleDOI
TL;DR: Intracellular dengue virus RNA from cells infected with transcript-derived virus contained an introduced BstEII site, proving that infectivity was derived from RNA transcripts and not from contamination with parental d Dengue virus.
Abstract: The dengue virus type 2 genomic RNA was amplified by reverse transcription-PCR and cloned as four cDNA fragments. We could not assemble these four fragments into full-length cDNA in Escherichia coli. The full-length dengue virus cDNA was constructed by homologous recombination in yeast, either as part of a yeast artificial chromosome or in a yeast-E. coli shuttle vector. Full-length cDNA clones were propagated once in E. coli to prepare useful quantities of DNA. In vitro transcription of these clones produced full-length RNA transcripts. Introduction of these transcripts into LLC-MK2 cells produced typical dengue infection, as judged by cytopathic effects and indirect immunofluorescence. Infectivity was sensitive to RNase digestion and was dependent on the presence of cap analog in the transcription reaction mixture. Virus in the medium was passaged on C6-36 cells to produce stocks, and these stocks had titers and plaque morphologies similar to those of the parental dengue virus type 2. Intracellular dengue virus RNA from cells infected with transcript-derived virus contained an introduced BstEII site, proving that infectivity was derived from RNA transcripts and not from contamination with parental dengue virus. Transcript-derived virus was comparable to dengue virus type 2 for growth and protein expression in tissue culture cells. Sequence analysis of the dengue virus cDNA in one full-length clone revealed only one unexpected silent mutation. By using yeast technology, it will be easy to introduce specific mutations into the dengue virus cDNA, allowing analysis of the virus phenotype in cells transfected with mutant transcripts.


Journal ArticleDOI
01 Apr 1997-Vaccine
TL;DR: To develop a nucleic acid vaccine against dengue type-2 virus, the PreM and 92% of the envelope (E) genes were cloned into different eukaryotic plasmid expression vectors (pkCMVint Polyli and pVR1012).

Journal ArticleDOI
TL;DR: Results strongly suggest that the 40- and 45-kDa surface proteins located on the surface of C6/36 cells are putative receptors or part of a receptor complex for dengue virus.
Abstract: Dengue viruses infect cells by attaching to a surface receptor, probably through the envelope (E) glycoprotein, located on the surface of the viral membrane. However, the identity of the dengue virus receptor in the mosquito and in mammalian host cells remains unknown. To identify and characterize the molecules responsible for binding dengue virus, overlay protein blot and binding assays were performed with labeled virus. Two glycoproteins of 40 and 45 kDa located on the surface of C6/36 cells bound dengue type 4 virus. Virus binding by total and membrane proteins obtained from trypsin-treated cells was inhibited, while neuraminidase treatment did not inhibit binding. Periodate treatment of cell proteins did not reduce virus binding, but it modified the molecular weight of the polypeptide detected by overlay assays. Preincubation of C6/36 cells with electroeluted 40- and 45-kDa proteins or with specific antibodies raised against these proteins inhibited virus binding. These results strongly suggest that the 40- and 45-kDa surface proteins are putative receptors or part of a receptor complex for dengue virus.

Journal Article
TL;DR: The objectives of this paper are to describe the epidemiology of chikungunya infection based on outbreak investigations carried out in Khon Kaen (July 1991), Nakorn Si Thammarat (July 1995), and Nong Khai Provinces (August 1995), all of which occurred during the rainy season.
Abstract: The first reported case of chikungunya virus diagnosed by serology in Thailand was in 1960 and the last one was in 1991. The disease surveillance system does not specifically include chikungunya cases and the signs and symptoms are similar to these of dengue fever/dengue hemorrhagic fever (DF/DHF), rubella, and fever of unknown origin (FUO); thus cases might often be reported under those diagnoses. During the rainy season of 1995 (Jun-Aug), there were at least 2 reported chikungunya outbreaks which might indicate that it is a re-emerging disease in Thailand. However, there is still limited information and knowledge on some aspects of this disease such as clinical manifestations, subclinical cases, duration of illness, complications, transmission, immunity, and reservoirs. Thus, the objectives of this paper are to describe the epidemiology of chikungunya infection based on outbreak investigations carried out in Khon Kaen (July 1991), Nakorn Si Thammarat (July 1995), and Nong Khai Provinces (August 1995). All three outbreaks occurred during the rainy season. The three most common clinical manifestations were fever with severe althralgia with maculopapular rash. Both sexes and all age groups were affected. Serological results were positive for IgM, with four-fold rises in paired sera, and viral isolation in Nakorn Si Thammarat and Nong Khai. Only in Nong Khai was hemagglutinin inhibition conducted and the results were positive. No deaths were reported. The outbreaks occurred in rural villages and all three larval indices (BI, HI, CI) were very high. The possible vectors in these outbreaks were Aedes aegypti and Aedes albopictus. In the Nong Khai outbreak, blood specimens were taken at the 3-5th day after onset and therefore the proportion of positive results was low. IgM antibody of follow-up cases declined within 3 months, villagers from all three areas with outbreaks mentioned that they had no previous experience of this disease. This suggests that chikungunya infection is a re-emerging disease.

Book
01 Jan 1997
TL;DR: Evolvability of Emerging Viruses Yellow Fever Dengue and other Viral Hemorrhagic Fevers Leptospirosis Human Immunodeficiency Virus Emerging Fungal Infections: Histoplasmosis, Phaeohyphomycosis, and Sporotrichosis
Abstract: Evolvability of Emerging Viruses Yellow Fever Dengue and other Viral Hemorrhagic Fevers Leptospirosis Human Immunodeficiency Virus Emerging Fungal Infections: Histoplasmosis, Phaeohyphomycosis, and Sporotrichosis Diphtheria Tuberculosis Mycobacterium avium Chancroid Meningococcal Disease Escherichia coli 0157:H7 Malaria: a Reemerging Disease Lymphatic Filariasis Epidemiology and Molecular Biology of Antimicrobial Resistance in Bacteria Emerging Infectious Agents and the Forensic Pathologist: the New Mexico Model Bovine Spongiform Encephalopathy and the Creuzfeldt-Jakob Variant Emerging Infections in Captive Wildlife

Journal ArticleDOI
TL;DR: Using a universal primer set designed to match the sequence of the NS1 gene of flaviviruses, the virus RNA of dengue, Japanese encephalitis, powassan and langat of Flaviviridae were successfully amplified by polymerase chain reaction (PCR) via cDNA; and with different internal primers, the serotypes of the d Dengue viruses were identified.
Abstract: Using a universal primer set designed to match the sequence of the NS1 gene of flaviviruses, the virus RNA of dengue (DEN), Japanese encephalitis (JEV), powassan and langat of Flaviviridae were successfully amplified by polymerase chain reaction (PCR) via cDNA; and with different internal primers, the serotypes of the dengue viruses were identified. Of the 78 clinically diagnosed dengue fever patients, 18 patients were positive for DEN 1, 48 patients for DEN 2 and 8 patients concurrently infected with DEN 4. Of the 52 patients admitted with Japanese encephalitis (JE), 45 were determined to be JEV infections. By nested PCR, we completed the identification of flaviviruses within 2 days. The results show that seven primers have a potential value for rapid clinical diagnosis of flavivirus infections.


Journal ArticleDOI
TL;DR: A reverse transcriptase-polymerase chain reaction (RT-PCR) method was developed as a rapid diagnostic test of dengue viremia and could be detected in a 6-hr assay by combining a silica method for RNA isolation and RT-PCRs.
Abstract: A reverse transcriptase-polymerase chain reaction (RT-PCR) method was developed as a rapid diagnostic test of dengue viremia. To detect dengue viruses in serum or plasma specimens, a pair of universal primers was designed for use in the RT-PCR. Using these primers, the 3′-noncoding region of dengue virus types 1, 2, 3, and 4 could be amplified, but not those of other flaviviruses, such as West Nile virus, Japanese encephalitis virus, and yellow fever virus, or the alphavirus Sindbis virus. The sensitivity of the RT-PCR assay was similar to that of a quantitative fluorescent focus assay of dengue viruses in cell culture. Combining a silica method for RNA isolation and RT-PCR dengue virus could be detected in a 6-hr assay. In a preliminary study using this method, we detected dengue virus in 38 of 39 plasma specimens from which dengue virus had been isolated by mosquito inoculation. We then applied this method for detecting dengue viremia to 117 plasma samples from 62 children with acute febrile illnesses in a dengue-endemic area. We detected dengue viremia in 19 of 20 samples obtained on the day of presentation, which had been confirmed as acute dengue infection by mosquito inoculation and antibody responses. The overall sensitivity of this method was 91.4% (32 of 35; 95% confidence interval [CI] = 82.2–100%). The results from testing plasma samples from febrile nondengue patients showed a specificity of 95.4% (42 of 44; 95% CI = 89.3–100%).

Journal ArticleDOI
21 May 1997-JAMA
TL;DR: Active surveillance, with clinical and laboratory evaluation directed by an epidemiologic team, led to the timely recognition of an outbreak of febrile illness among US troops in Haiti.
Abstract: Objective. —To describe clinical manifestations and public health implications of an outbreak of dengue fever (DF) during Operation Uphold Democracy, Haiti, 1994. Design. —Consecutive sample. Setting. —Military combat support hospital, Port-au-Prince, Haiti. Patients. —A total of 101 US military personnel with acute febrile illnesses. Interventions. —A disease surveillance team collected clinical and epidemiologic data from US military clinics throughout Haiti. Febrile patients admitted to the combat support hospital were evaluated with standardized clinical and laboratory procedures. The surveillance team followed patients daily. Main Outcome Measures. —Arbovirus isolation and specific antibody determination and symptoms and physical findings. Results. —Febrile illnesses accounted for 103 (25%) of the 406 combat support hospital admissions during the first 6 weeks of deployment. All patients with febrile illness recovered. A total of 30 patients had DF; no patient had evidence of infection with malaria. Dengue virus serotypes 1,2, and 4 were isolated from 22 patients, and 8 patients developed IgM antibody to dengue virus. Patients with DF could not be distinguished from other febrile patients on clinical grounds alone. No arboviruses other than dengue were identified. Conclusions. —Active surveillance, with clinical and laboratory evaluation directed by an epidemiologic team, led to the timely recognition of an outbreak of febrile illness among US troops in Haiti. Viral isolation and serological studies were essential in confirming DF. During the surveillance period, DF accounted for at least 30% of the febrile illnesses among hospitalized US troops. Dengue fever is a significant threat to military personnel and civilian travelers in Haiti and has the potential for introduction to and transmission in the United States.

Journal ArticleDOI
TL;DR: In this article, the authors describe the reappearance of dengue serotype 3 in the Americas, following a 17-year absence, through the recent experience of Nicaragua, and describe the most frequent symptoms of 18 patients diagnosed with hemorrhagic manifestations were fever, headache, vomiting, myalgia, arthralgia, and epistaxis.
Abstract: The principal aim of the report presented here is to describe the reappearance of dengue serotype 3 in the Americas, following a 17-year absence, through the recent experience of Nicaragua. In all, 356 serum samples obtained through Nicaragua's dengue monitoring system in October 1994 during an epidemic were examined. Anti-dengue IgM antibodies were detected in 43% of these, with sera from 12 of the 18 areas covered by Nicaragua's local integrated health care systems yielding positive results. In addition, dengue virus was isolated from 5 of 24 sera obtained from patients with hemorrhagic symptoms, dengue 3 being isolated from 3 of these samples and dengue 1 from the other 2. A diagnosis of dengue with hemorrhagic manifestations or of hemorrhagic dengue was supported or confirmed by laboratory findings obtained from 26 of 39 patients hospitalized in Leon or Managua. The most frequent symptoms of 18 patients diagnosed as having dengue with hemorrhagic manifestations were fever, headache, vomiting, myalgia, arthralgia, and epistaxis. The remaining eight patients, diagnosed as having probable hemorrhagic dengue, exhibited fever, general malaise, hemorrhaging, thrombocytopenia, hemoconcentration, and hemagglutination-inhibition antibody titers ranging from 640 to 20 480. Overall, the reappearance of dengue serotype 3 in the Region was confirmed, together with its ability to produce cases of hemorrhagic dengue. At least in Nicaragua, it is apparent that the introduction of dengue serotype 3 has prompted an increase in the number of classical dengue and hemorrhagic dengue cases, a scenario that might constitute the grim prelude to future developments in the Americas if urgent attention is not given to controlling the disease's mosquito vector.

Journal Article
TL;DR: Until the dengue vaccine is commercially available for mass immunisation of the population, community-based integrated control of Aedes aegypti remains the key to the prevention and control of DF/DHF.
Abstract: Despite its well-established integrated nationwide Aedes mosquito control programme which incorporates source reduction, public health education and law enforcement, Singapore has not been spared from the regional resurgence of dengue. The disease incidence has been increasing from 9.3 per 100,000 in 1988 to 102.7 per 100,000 in 1996 at the time when the Aedes house index (HI) has dropped to around 1% from > 25% in the 1960s. Majority of the cases reported from 1990 to 1996 were dengue fever (DF); dengue haemorrhagic fever (DHF) constituted only 6.7%. The case-fatality rate was 0.1% with 13 (81.3%) of 16 serologically confirmed deaths above 19 years of age. The median age has shifted from 14 years in 1973 to 27 years in 1996. The proportion of primary infections also increased from about one-third in 1990 to nearly half in 1996. All four dengue serotypes have been detected from infected persons with dengue 2 predominating in 1990, 1991 and 1993, dengue 3 in 1992 and 1994 and dengue 1 in 1995 and 1996. The disease incidence was significantly correlated with Aedes aegypti HI and residents of compound houses had a significantly higher rate of infection as well as a higher morbidity rate compared with dwellers of high-rise public housing estates. Seroprevalence surveys confirmed the low level of dengue transmission. The immunity level of the general population has been declining with only 6.4% of children and young adults below 25 years of age possessing haemagglutination-inhibition antibody to dengue 2. It would appear that the successful vector control programme over the last two decades has brought about a paradoxical situation in that outbreaks tend to occur more frequently and with even greater intensity because of the low herd immunity of the population. Until the dengue vaccine is commercially available for mass immunisation of the population, community-based integrated control of Aedes aegypti remains the key to the prevention and control of DF/DHF.

Journal ArticleDOI
TL;DR: A 15-year-old European boy, who had been in Kenya for 1 month, was admitted to the hospital with a 3-day history of headache, malaise, anorexia, fever, and vomiting, and his condition steadily deteriorated, and he died on the 11th day of illness.