Showing papers on "Dengue fever published in 1998"

Dengue and Dengue Hemorrhagic Fever

Abstract: Dengue fever, a very old disease, has reemerged in the past 20 years with an expanded geographic distribution of both the viruses and the mosquito vectors, increased epidemic activity, the development of hyperendemicity (the cocirculation of multiple serotypes), and the emergence of dengue hemorrhagic fever in new geographic regions. In 1998 this mosquito-borne disease is the most important tropical infectious disease after malaria, with an estimated 100 million cases of dengue fever, 500,000 cases of dengue hemorrhagic fever, and 25,000 deaths annually. The reasons for this resurgence and emergence of dengue hemorrhagic fever in the waning years of the 20th century are complex and not fully understood, but demographic, societal, and public health infrastructure changes in the past 30 years have contributed greatly. This paper reviews the changing epidemiology of dengue and dengue hemorrhagic fever by geographic region, the natural history and transmission cycles, clinical diagnosis of both dengue fever and dengue hemorrhagic fever, serologic and virologic laboratory diagnoses, pathogenesis, surveillance, prevention, and control. A major challenge for public health officials in all tropical areas of the world is to devleop and implement sustainable prevention and control programs that will reverse the trend of emergent dengue hemorrhagic fever.

Dengue fever epidemic potential as projected by general circulation models of global climate change

Abstract: Climate factors influence the transmission of dengue fever, the world's most widespread vector-borne virus. We examined the potential added risk posed by global climate change on dengue transmission using computer-based simulation analysis to link temperature output from three climate general circulation models (GCMs) to a dengue vectorial capacity equation. Our outcome measure, epidemic potential, is the reciprocal of the critical mosquito density threshold of the vectorial capacity equation. An increase in epidemic potential indicates that a smaller number of mosquitoes can maintain a state of endemicity of disease where dengue virus is introduced. Baseline climate data for comparison are from 1931 to 1980. Among the three GCMs, the average projected temperature elevation was 1.16 degrees C, expected by the year 2050. All three GCMs projected a temperature-related increase in potential seasonal transmission in five selected cities, as well as an increase in global epidemic potential, with the largest area change occurring in temperate regions. For regions already at risk, the aggregate epidemic potential across the three scenarios rose on average between 31 and 47% (range, 24-74%). If climate change occurs, as many climatologists believe, this will increase the epidemic potential of dengue-carrying mosquitoes, given viral introduction and susceptible human populations. Our risk assessment suggests that increased incidence may first occur in regions bordering endemic zones in latitude or altitude. Endemic locations may be at higher risk from hemorrhagic dengue if transmission intensity increases.

Typing of dengue viruses in clinical specimens and mosquitoes by single-tube multiplex reverse transcriptase PCR

Abstract: In recent years, dengue viruses (serotypes 1 to 4) have spread throughout tropical regions worldwide. In many places, multiple dengue virus serotypes are circulating concurrently, which may increase the risk for the more severe form of the disease, dengue hemorrhagic fever. For the control and prevention of dengue fever, it is important to rapidly detect and type the virus in clinical samples and mosquitoes. Assays based on reverse transcriptase (RT) PCR (RT-PCR) amplification of dengue viral RNA can offer a rapid, sensitive, and specific approach to the typing of dengue viruses. We have reduced a two-step nested RT-PCR protocol to a single-tube reaction with sensitivity equivalent to that of the two-step protocol (1 to 50 PFU) in order to maximize simplicity and minimize the risk of sample cross-contamination. This assay was also optimized for use with a thermostable RT-polymerase. We designed a plasmid-based internal control that produces a uniquely sized product and can be used to control for both reverse transcription or amplification steps without the risk of generating false-positive results. This single-tube RT-PCR procedure was used to type dengue viruses during the 1995 and 1997-1998 outbreaks in Nicaragua. In addition, an extraction procedure that permits the sensitive detection of viral RNA in pools of up to 50 mosquitoes without PCR inhibition or RNA degradation was developed. This assay should serve as a practical tool for use in countries where dengue fever is endemic, in conjunction with classical methods for surveillance and epidemiology of dengue viruses.

Exploratory space-time analysis of reported dengue cases during an outbreak in Florida, Puerto Rico, 1991-1992.

Abstract: The spatial and temporal distributions of dengue cases reported during a 1991-1992 outbreak in Florida, Puerto Rico (population = 8,689), were studied by using a Geographic Information System. A total of 377 dengue cases were identified from a laboratory-based dengue surveillance system and georeferenced by their residential addresses on digital zoning and U.S. Geological Survey topographic maps. Weekly case maps were generated for the period between June and December 1991, when 94.2% of the dengue cases were reported. The temporal evolution of the epidemic was rapid, affecting a wide geographic area within seven weeks of the first reported cases of the season. Dengue cases were reported in 217 houses; of these 56 (25.8%) had between two and six reported cases. K-function analysis was used to characterize the spatial clustering patterns for all reported dengue cases (laboratory-positive and indeterminate) and laboratory-positive cases alone, while the Barton and David and Knox tests were used to characterize spatio-temporal attributes of dengue cases reported during the 1991-1992 outbreak. For both sets of data significant case clustering was identified within individual households over short periods of time (three days or less), but in general, the cases had spatial pattern characteristics much like the population pattern as a whole. The rapid temporal and spatial progress of the disease within the community suggests that control measures should be applied to the entire municipality, rather than to the areas immediately surrounding houses of reported cases. The potential for incorporating Geographic Information System technologies into a dengue surveillance system and the limitations of using surveillance data for spatial studies are discussed.

Reemergence of dengue in Cuba: A 1997 epidemic in Santiago de Cuba.

Abstract: After 15 years of absence dengue reemerged in 1997 in the municipality of Santiago de Cuba Cuba. After the 1981 epidemic in which there were 10312 cases of dengue hemorrhagic fever/dengue shock syndrome and 158 deaths a campaign to improve mosquito control and eradicate Aedes aegypti was launched and most of Cubas 169 municipalities were free of the vector. The municipality of Santiago de Cuba was reinfested in 1992 by A. aegypti transported in imported tires. Risk factors in the province include limited water supply inadequate eradication efforts high vector infestation and increasing migration of people from endemic countries of Latin America and the Caribbean. Establishment of an active dengue surveillance system in 1997 identified 205 cases of dengue hemorrhagic fever 12 of which were fatal. Secondary infection was implicated in 98% of these cases. No autochthonous transmission to other municipalities has been detected. As a result of the 1997 epidemic an epidemiological alert system has been established and antivector intervention and seroepidemiological surveillance have been strengthened throughout Cuba.

Using disability-adjusted life years to assess the economic impact of dengue in Puerto Rico: 1984-1994.

Abstract: This study presents the disability-adjusted life years (DALYs), a non-monetary economic measure of impact, lost to dengue in Puerto Rico for the period 1984-1994. Data on the number of reported cases, cases with hemorrhagic manifestations, hospitalizations, and deaths were obtained from a surveillance system maintained at the Dengue Branch, Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention (San Juan, PR). The reported cases were divided into two age groups (0-15 years old and >15 years old), and then multiplied by predetermined factors (10 for 0-15 years; 27 for >15 years) to allow for age-related under-reporting of cases. Severity of dengue was modeled by classifying cases into three groups: dengue fever, dengue with severe manifestations, and hospitalized cases. Each group was assigned a different number of days lost because of dengue-related disability. Dengue caused an average of 658 DALYs per year per million population (SE = 114, range = 145-1,519). A multivariate sensitivity analysis, which simultaneously altered the values of six input variables, produced a mean of 580 DALYs/year/million population, with a maximum average of 1,021 DALYs/year/million population, and a maximum, single-year estimate for 1994 of 2,153 DALYs/million population. The most important input was the number of days lost to classic dengue. The DALYs/year/million population lost to dengue in Puerto Rico are much greater than previous estimates concerning the impact of dengue hemorrhagic fever alone. The loss to dengue is similar to the losses per million population in the Latin American and Caribbean region attributed to any of the following diseases or disease clusters; the childhood cluster (polio, measles, pertussis, diphtheria, tetanus), meningitis, hepatitis, or malaria. The loss is also of the same order of magnitude as any one of the following: tuberculosis, sexually transmitted diseases (excluding human immunodeficiency virus), tropical cluster (e.g., Chagas' disease, leishmaniasis), or intestinal helminths. The results objectively suggest that when governments and international funding agencies allocate resources for research and control, dengue should be given a priority equal to many other infectious diseases that are generally considered more important.

Monitoring of dengue viruses in field-caught Aedes aegypti and Aedes albopictus mosquitoes by a type-specific polymerase chain reaction and cycle sequencing.

Abstract: Virologic surveillance for dengue through the detection of the prevalent serotype(s) circulating in the human population during inter- and intra-epidemic periods constitutes a reliable sentinel system for dengue outbreaks. We have applied a rapid and sensitive, semi-nested, reverse transcription-polymerase chain reaction (RT-PCR) assay using nonstructural protein 3 gene primers for the type-specific-detection of dengue viruses in artificially infected and in field-caught adult Aedes mosquitoes. In laboratory experiments, the assay was sensitive enough to detect one virus-infected mosquito head in pools of up to 59 uninfected heads. In a prospective field study conducted from April 1995 to July 1996, female adult Ae. aegypti and Ae. albopictus mosquitoes were caught from selected dengue-sensitive areas in Singapore and assayed by RT-PCR. Approximately 20% of 309 mosquito pools were positive for dengue viruses. Of the 23 RT-PCR-positive Ae. aegypti pools (containing 1-17 mosquitoes each), 18 pools (78.3%) were positive for dengue 1 virus. There were 40 RT-PCR-positive Ae. albopictus pools (containing 1-33 mosquitoes each) of which 31 (77.5%) were positive for dengue 1 virus. The predominant virus type responsible for the current dengue epidemic since 1995 was also dengue 1. The geographic locations of the virus-infected mosquitoes correlated with the residences or workplaces of patients within dengue outbreak areas. A total of 43.5% of the positive Ae. aegypti pools and 25.0% of the positive Ae. albopictus pools contained only a single mosquito. Both Aedes species showed similar overall minimum infection rates of 57.6 and 50 per 1,000 mosquitoes. Infected Ae. aegypti were detected as early as six weeks before the start of the dengue outbreaks in 1995 and 1996. However, infected Ae. albopictus appeared later, when the number of cases was increasing. Virologic surveillance by RT-PCR for detecting dengue virus-infected Aedes mosquitoes in the field may serve as an early warning monitoring system for dengue outbreaks.

Pathophysiologic and prognostic role of cytokines in dengue hemorrhagic fever

Abstract: Dengue shock syndrome is a severe complication of dengue hemorrhagic fever (DHF), characterized by a massive increase in vascular permeability. Plasma cytokine concentrations were prospectively studied in 443 Vietnamese children with DHF, of whom 6 died. Shock was present in 188 children on admission to hospital, and in 71 children it developed later. Contrary to expectations, certain inflammatory markers (interleukin-6 and soluble intercellular adhesion molecule-1) were lower in the group with shock, and this may reflect the general loss of protein from the circulation due to capillary leakage. Only soluble tumor necrosis factor receptor (TNFR) levels showed a consistent positive relationship with disease severity. In patients with suspected DHF without shock, admission levels of sTNFR-75 in excess of 55 pg/mL predicted the subsequent development of shock, with a relative risk of 5.5 (95% confidence interval, 2.3 ‐ 13.2). Large-scale release of soluble TNFR may be an early and specific marker of the endothelial changes that cause dengue shock syndrome.

The global pandemic of dengue/dengue haemorrhagic fever: current status and prospects for the future.

Abstract: Dengue/dengue haemorrhagic fever has been one of the most important resurgent tropical diseases in the past 17 years, with expanding geographic distribution of both the viruses and the mosquito vectors, increased frequency of epidemics, the development of hyperendemicity (co-circulation of multiple virus serotypes) and the emergence of dengue haemorrhagic fever in new areas. This paper briefly reviews the changing epidemiology of dengue, discusses some of the factors responsible for the recent resurgence, and reviews the current options for reversing the trend of emergent disease.

Elevated levels of IL-8 in dengue hemorrhagic fever

Abstract: Dengue virus causes dengue fever, a mild febrile illness, and at times dengue hemorrhagic fever (DHF), a severe illness the pathogenesis of which is not fully understood. Given the crucial roles played by interleukin-8 (IL-8) as a chemoattractant cytokine and in inflammatory processes, levels of circulating IL-8 in the sera and IL-8 mRNA in the peripheral blood mononuclear cells (PBMC) were measured in 99 patients of a recent dengue epidemic that occurred in India in 1996 and in 21 normal healthy controls. Twenty-six of the patients had dengue fever (DF) and the remaining 73 were diagnosed as having different grades of DHF. All the control normal sera were negative for IL-8, so were their PBMC for IL-8 mRNA. Increased levels of IL-8 in the sera and IL-8 mRNA in their PBMC were observed in patients with severe illness of DHF grades III and IV. Only two out of 26 patients of DF and one out of 10 DHF grade I patient were positive for IL-8 and all three deteriorated to DHF grade IV within 24 hr. All six patients of DHF grade IV who died had higher serum level of IL-8 above 200 pg/ml, the highest being 5,568 pg/ml in one patient; the presence of mRNA for IL-8 was very high in all patients. A striking correlation was observed between increased levels of IL-8 and severe DHF, with greater levels in patients with increased grade of the disease and death. These results suggest that IL-8 may have an important role and may be an indicator of increasing severity of the disease and death.

Dengue virus in the brain of a fatal case of hemorrhagic dengue fever

Abstract: Neurologic complications associated with dengue fever are in general unusual. However, recent reports evidence more frequent neurologic alterations. In Mexico, neurologic involvement has not been reported in dengue cases. This report demonstrates the detection of dengue virus in the brain of a fatal case of dengue hemorrhagic fever. Serotype 4 was detected by immunohistochemistry and by RT-PCR in the inferior olivary nucleus of medulla and in the granular layer of cerebellum. Immunoreactivity was observed in neurons, astrocytes, microglia and endothelial cells. Our results emphasize the importance of neurologic manifestations in patients with dengue fever.

An epidemic of dengue hemorrhagic fever and dengue shock syndrome in children in Delhi.

Abstract: The aim was to study clinical profiles and outcome of children of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) during 1996 Delhi epidemic. Children hospitalized from September to November 1996 were studied. All patients were diagnosed managed and monitored according to a standard protocol. 134 children (80 (60%) males and 54 (40%) females) were studied. 60 (45%) children were 1:160) for dengue type 2 in 31 (80%) of 39 patients in whom sera was tested during the acute phase of illness. Mortality was 6%. Hematocrit >40% was observed in only 25 (18%) patients and hence the management protocol was based on clinical signs and symptoms and not on hematocrit. A management protocol of DHF/DSS in which fluid therapy is not based on hematocrit values needs to be formulated. (authors)

Predominance of HLA-restricted cytotoxic T-lymphocyte responses to serotype-cross-reactive epitopes on nonstructural proteins following natural secondary dengue virus infection

Abstract: We examined the memory cytotoxic T-lymphocytic (CTL) responses of peripheral blood mononuclear cells (PBMC) obtained from patients in Thailand 12 months after natural symptomatic secondary dengue virus infection. In all four patients analyzed, CTLs were detected in bulk culture PBMC against nonstructural dengue virus proteins. Numerous CD4+ and CD8+ CTL lines were generated from the bulk cultures of two patients, KPP94-037 and KPP94-024, which were specific for NS1.2a (NS1 and NS2a collectively) and NS3 proteins, respectively. All CTL lines derived from both patients were cross-reactive with other serotypes of dengue virus. The CD8+ NS1.2a-specific lines from patient KPP94-037 were HLA B57 restricted, and the CD8+ NS3-specific lines from patient KPP94-024 were HLA B7 restricted. The CD4+ CTL lines from patient KPP94-037 were HLA DR7 restricted. A majority of the CD8+ CTLs isolated from patient KPP94-024 were found to recognize amino acids 221 to 232 on NS3. These results demonstrate that in Thai patients after symptomatic secondary natural dengue infections, CTLs are mainly directed against nonstructural proteins and are broadly cross-reactive.

Evaluation of a Rapid Immunochromatographic Test for Diagnosis of Dengue Virus Infection

Abstract: A rapid (<7-min) immunochromatographic test for immunoglobulin M (IgM) and IgG antibodies to dengue viruses was evaluated by using hospital admission and discharge sera from 124 patients. The reference laboratory diagnosis was based on the results of virus isolation, hemagglutination-inhibition assay (HAI), and enzyme immunoassay (EIA). By the standard assays, patients experienced primary dengue virus infection (n = 30), secondary dengue virus infection (n = 48), Japanese encephalitis (JE) virus infection (n = 20), or no flavivirus infection (n = 26). The rapid test demonstrated 100% sensitivity in the diagnosis of dengue virus infection and was able to distinguish between primary and secondary dengue virus infections through the separate determinations of IgM and IgG. For all patients with primary dengue virus infection a positive test for IgM to dengue virus and a negative test for IgG to dengue virus were obtained, whereas for 46 of 48 patients (96%) with secondary dengue virus infection, a positive test for IgG to dengue virus with or without a positive test for IgM to dengue virus was obtained. The remaining two patients with secondary dengue virus infection had positive IgM test results and negative IgG test results. Furthermore, the rapid test was positive for patients confirmed to be infected with different dengue virus serotypes (12 infected with dengue virus serotype 1, 4 infected with dengue virus serotype 2, 3 infected with dengue virus serotype 3, and 2 infected with dengue virus serotype 4). The specificity of the test for nonflavivirus infections was 88% (3 of 26 positive), while for JE virus infections the specificity of the test was only 50% (10 of 20). However, most patients with secondary dengue virus infection were positive for both IgM and IgG antibodies to dengue virus, while no patients with JE virus infection had this profile, so cross-reactivity was only a concern for a small proportion of patients with secondary dengue infections. The rapid test demonstrated a good correlation with the reference EIA and HAI and should be useful for the rapid diagnosis of dengue virus infections.

Molecular evolution of dengue type 2 virus in Thailand.

Abstract: Dengue is a mosquito-borne viral infection that in recent years has become a major international public health concern. Dengue hemorrhagic fever (DHF), first recognized in Southeast Asia in the 1950s, is today a leading cause of childhood death in many countries. The pathogenesis of this illness is poorly understood, mainly because there are no laboratory or animal models of disease. We have studied the genetic relationships of dengue viruses of serotype 2, one of four antigenically distinct dengue virus groups, to determine if viruses obtained from cases of less severe dengue fever (DF) have distinct evolutionary origins from those obtained from DHF cases. A very large number (73) of virus samples from patients with DF or DHF in two locations in Thailand (Bangkok and Kamphaeng Phet) were compared by sequence analysis of 240 nucleotides from the envelope/nonstructural protein 1 (E/NS1) gene junction of the viral genome. Phylogenetic trees generated with these data have been shown to reflect long-term evolutionary relationships among strains. The results suggest that 1) many different virus variants may circulate simultaneously in Thailand, thus reflecting the quasispecies nature of these RNA viruses, in spite of population immunity; 2) viruses belonging to two previously distinct genotypic groups have been isolated from both DF and DHF cases, supporting the view that they arose from a common progenitor and share the potential to cause severe disease; and 3) viruses associated with the potential to cause DHF segregate into what is now one, large genotypic group and they have evolved independently in Southeast Asia for some time.

Arboviruses in the Australian region, 1990 to 1998.

Abstract: Arboviruses continue to be major human pathogens in the Australian region. This report provides a summary of the activities of these viruses over the past eight years, and comments on new findings relevant to their respective ecologies. Of particular interest and concern is the propensity of these viruses to spread. The examples discussed include the initiation of dengue epidemics in north Queensland by virus imported in viraemic travellers; the spread of Japanese encephalitis virus to the Australasian region and its probable enzootic establishment in the south-west of Papua New Guinea; the potential spread of Ross River virus to other countries, as demonstrated by the 1979-80 outbreak in the South Pacific, and the recent occurrence in military personnel from the United States of America after an exercise; and the recent spread of Barmah Forest virus into Western Australia.

The effect of temperature and humidity on dengue virus propagation in Aedes aegypti mosquitos.

Abstract: The effect of temperature and relative humidity on dengue virus propagation in the mosquito as one of the possible contributing factors to dengue hemorrhagic fever (DHF) outbreaks was studied. Ae. aegypti mosquitos were reared under standard conditions and inoculated intrathoracically with dengue virus. Virus propagation in the mosquitos was determined at the temperature and relative humidity of all 3 seasons of Yangon and for the simulated temperature and relative humidity of Singapore. The virus propagation was detected by direct fluorescent antibody technique (DFAT) with mosquito head squash and the virus titer was determined by plaque forming unit test (PFUT) in baby hamster kidney-21 cells. The results show that the infected mosquitos kept under the conditions of the rainy season and under the simulated conditions of Singapore had a significantly higher virus titer (p=<0.05) when compared with the other 2 seasons of Yangon. So it is thought that the temperature and relative humidity of the rainy season of Yangon and that of Singapore favors dengue virus propagation in the mosquito and is one of the contributing factors to the occurence of DHF outbreaks.

Epidemic Dengue and Dengue Hemorrhagic Fever: a Global Public Health Problem in the 21st Century

Abstract: Dengue fever and dengue hemorrhagic fever (DHF) are caused by infection with four dengue virus serotypes, dengue-1 (DEN-1), DEN-2, DEN-3 and DEN-4, which are closely related to each other antigenically. This chapter reviews the changing epidemiology associated with dengue viruses and attempts to explain why changes have occurred in the waning years of the 20th century. The reasons for the dramatic resurgence of epidemic dengue/DHF in the waning years of the 20th century are complex and not fully understood but are most likely associated with demographic and societal changes that have occurred over the past 50 years. The emphasis has thus been on implementing emergency control methods in response to epidemics rather than on developing programs to prevent epidemic transmission. This approach has been particularly detrimental to dengue prevention and control because in most countries surveillance is very poor; the passive surveillance systems relied on to detect increased transmission are dependent on reports by local physicians, who often have a low index of suspicion and do not consider dengue in their differential diagnosis of dengue-like illness. As a result, the epidemic has often reached or passed peak transmission before it is detected, and emergency control measures are nearly always implemented too late to have any impact on the course of the epidemic. Only with an improved public health infrastructure to support community-based prevention programs will we be able to reverse the trend of emergent epidemic dengue/DHF.

Effect of size and geographic origin of Aedes aegypti on oral infection with dengue-2 virus.

Abstract: Differences in larval habitats cause variation in the size of Aedes aegypti (L.) adults. We suspected that such size variation was related to the ease with which the mosquitoes could be infected with dengue virus. Using a rearing procedure that produced three distinct size classes of mosquitoes, we determined the percentage of mosquitoes that developed disseminated dengue-2 infection following oral feeding with a suspension containing 3.3 x 10(7) plaque-forming units/ml. Mosquitoes were reared from eggs deposited by females captured in either of two villages in Chachoengsao Province or in Bangkok, Thailand. More of the larger mosquitoes (10.7%) were infected than the medium (5.6%) or small (5.7%) mosquitoes. Mosquitoes from Bangkok were less easily infected (5.0%) than mosquitoes from either of the two villages (8.5% and 10.7%). These results suggest that quantitative risk assessment of dengue transmission may be very difficult unless inoculation rate is measured directly. Also, control procedures that reduce density of larvae in individual containers may exacerbate dengue transmission by creating larger mosquitoes that are more easily infected.

Evaluation of the protective efficacy of a recombinant dengue envelope B domain fusion protein against dengue 2 virus infection in mice.

Abstract: A recombinant protein containing part of the dengue (DEN) 2 envelope protein was evaluated as a subunit immunogen for vaccination against DEN virus infection. A gene fragment encoding amino acids 298-400 (B domain) of the DEN-2 virus envelope was expressed as a fusion protein with the maltose binding protein (MBP) of Escherichia coli. This recombinant, DEN-2(B)/MBP, was purified and analyzed for its antigenicity, immunogenicity, and ability to protect mice against lethal challenge. The recombinant antigen reacted with a DEN-2 type-specific neutralizing monoclonal antibody (3H5), DEN-2 hyperimmune mouse ascitic fluid, and DEN-2 immune human sera. When administered to mice, DEN-2(B)/MBP elicited a DEN-2 virus neutralizing antibody response that conferred partial protection against challenge infection with a lethal dose of DEN-2 virus administered by intracranial inoculation. In addition, no replication of DEN-2 virus was detectable in the brains of the immunized mice as compared with control mice that were killed six days after challenge. Sera from immunized mice revealed no cross-neutralizing antibody to any of the other DEN serotypes in the plaque-reduction neutralization test. These findings warrant further studies with the DEN-2(B)/MBP antigen as a potential human vaccine candidate. An effective vaccine could prevent thousands of cases of illness and many deaths each year resulting from DEN virus infections.

Myocardial dysfunction in children with dengue haemorrhagic fever

Abstract: Background. Dengue fever/dengue haemorrhagic fever/ dengue shock syndrome is a serious health problem in tropical countries. Intravascular fluid depletion due to capillary leak is presumed to be the cause of hypotension in dengue haemorrhagic fever. The treatment guidelines of the World Health Organization lay stress primarily on monitoring and fluid replacementtherapy. During the 1996 epidemic in New Delhi, we observed problems in fluid management of such children and prospectively looked for myocardial dysfunction as an additional factor for hypotension. Methods. Fifty-four children «12 years old) admitted to the All India Institute of Medical Sciences, New Delhi after 15 October 1996 with various grades of the disease, who were fit to be shifted to the echocardiography laboratory, were examined clinically and subjected to a detailed M-mode, 2-dimensional and colour doppler echocardiography. Ejection fractions (TeichholzIModified Simpson's) and shortening fractions were calculated. Results. Ejection fraction by modified Simpson's rule was reduced «50%) in 9/54 (16.7%) children; 2 of these had significant reductions «35%). These 9 children belonged to all stages of clinical severity. Three of these 9 children who had a repeat echocardiogram within 2 months of the illness had improved ejection fractions. Conclusion. The role of myocardial dysfunction remains to be defined as there was no correlation with clinical severity. Myocardial functions need to be assessed in patients with this disease, especially those who have persistent hypotension in spite of adequate hydration. Natl Med J India 1998;11:59-61

Two contiguous outbreaks of dengue type 2 in north Queensland

Abstract: Objectives: To investigate two outbreaks of dengue type 2 in north Queensland, one in the Torres Strait beginning in late 1996, the other in a Cairns suburb in early 1997. Design: Epidemiological investigation of all laboratory-confirmed cases of dengue, entomological investigation of the local environment, and laboratory analysis of the isolated dengue viruses. Main outcome measures: Numbers of confirmed and of locally acquired cases; virus serotype; comparison of nucleotide sequences between viruses isolated from the two outbreaks; and Breteau Index (BI = number of containers with larvae of the mosquito vector Aedes aegypti found per 100 houses investigated) on the affected islands and in the Cairns suburb. Results: There were 201 confirmed cases of dengue in the Torres Strait outbreak, which lasted nearly seven months, and seven confirmed cases in the Cairns outbreak, which lasted about nearly 11 weeks. Most (190) were confirmed as dengue type 2. Nucleotide sequencing of viruses isolated from the two outbreaks showed they were identical. Ae. aegypti breeding sites were very common on the five Torres Strait islands surveyed (Bls, 73-219 - high risk), but less so in the Cairns suburb (BI, 23). The most common breeding sites were water storage reservoirs, particularly rainwater tanks, on the outer Torres Strait islands, discarded containers (such as plastic containers, buckets and tyres) on Thursday Island, and garden items (such as flowerpot bases and jars) in Cairns. Conclusions: The virus responsible for the Cairns outbreak was most probably introduced from the Torres Strait, whereas the virus responsible for the Torres Strait outbreak was imported from Papua New Guinea. Preventive strategies tailored to specific locations are needed to reduce breeding of Ae. aegypti in north Queensland, and the consequent risk of future outbreaks of dengue.

Immunoglobulin A-Specific Capture Enzyme-Linked Immunosorbent Assay for Diagnosis of Dengue Fever

Abstract: Dengue fever (DF) is usually diagnosed by testing for dengue virus immunoglobulin M (IgM) by a capture enzyme-linked immunosorbent assay (ELISA) (MAC-ELISA). However, IgM can last for months, and its presence might reflect a previous infection. We have tested the use of anti-dengue virus IgA capture ELISA (AAC-ELISA) for the diagnosis of DF by comparing the results of MAC-ELISAs and AAC-ELISAs for 178 serum samples taken from patients with confirmed cases of DF. IgM appears more rapidly (mean delay of positivity, 3.8 days after the onset of DF) than IgA (4.6 days) but lasts longer; the peak IgA titer is obtained on day 8. The specificity and the positive predictive value of AAC-ELISA are 100%; its sensitivity and negative predictive value (NPV) are also 100% between days 6 and 25 after the onset of DF, but they decrease drastically when data for tests conducted with specimens from the first days of infection are included, because the IgA titers, like the IgM titers, have not yet risen. AAC-ELISA is a simple method that can be performed together with MAC-ELISA and that can help in interpreting DF serology.

Molecular biology of dengue virus

Abstract: In Venezuela the problem of Dengue infection has become worst during the last decade, turning the country into an hyperendemic region where three of the four serotypes co-circulate. The Dengue has become a problem of Public Health, so the knowledge of the virus, its life cycle and characteristics, as well as the different aspects related with its biology are extremely important to fight the virus and for the develop of a vaccine. In a general way, the present work describes different aspects related to the molecular biology of the Dengue virus and its life cycle: the structure, composition, production of structural and non structural protein and its relation to the replication cycle of the virus. Some aspects related with the assembly and release of particles from infected cells are also discussed. With this a general view of the molecular biology of the Dengue virus and its replication in the host cell is shown.

Dengue virus infection among children with undifferentiated fever in Karachi.

Abstract: Sera were collected from a total of 122 children, comprising 117 cases with undifferentiated fever and 5 cases with dengue hemorrhagic fever (DHF), during June to September 1994 in Karachi, Pakistan. Sera were tested by the IgM-capture ELISA using dengue type 1 (D1), dengue type 2 (D2), West Nile (WN), and Japanese encephalitis (JE) viral antigens. Among 92 single sera from undifferentiated fever cases, IgM antibodies were detected in 5 cases by D1, 8 cases by D2, and 5 cases by WN antigens, respectively. Corresponding number of positives among 25 paired sera from undifferentiated fever cases were 3 by D1, 6 by 02, and 1 by WN antigen. Four out of 5 DHF cases possessed anti-D1 as well as anti-D2 IgM antibodies. Only a single DHF case was positive for anti-WN IgM antibodies. Anti-JE IgM antibodies were not detected in any of the tested serum specimens.